Safety and Efficacy of Linaclotide in Patients With Chronic Constipation and Prominent Abdominal Bloating

Phase 3

Completed

Conditions: Chronic Constipation
Constipation

Interventions: Drug: Linaclotide 290 micrograms
Drug: Matching placebo
Drug: Linaclotide 145 micrograms

Registration Number: NCT01642914

Lead Sponsor: Forest Laboratories

Brief Summary: The purpose of this study is to evaluate the efficacy and safety of linaclotide compared with placebo in patients with chronic constipation (CC) and prominent abdominal bloating. This study includes an up to 3-week screening period and a 2-3 week pretreatment period. Patients who are eligible will be randomized to one of two doses of linaclotide or placebo for 12 weeks. This 12-week study will assess the effects of linaclotide on bowel movement frequency, as well as other abdominal and bowel symptoms of CC.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 487

Inclusion Criteria

Patient has completed a colonoscopy according to the American Gastroenterological Association criteria with no clinically significant findings
Patient has successfully completed protocol procedures (with no clinically significant findings)
Patient meets protocol criteria for Chronic Constipation(CC): < 3 bowel movements per week and reports one or more of the following symptoms for at least 12 weeks:
1. Straining during more than 25% of BMs
2. Lumpy or hard stools during more than 25% of BMs
3. Sensation of incomplete evacuation during more than 25% of BMs
Patient demonstrates continued chronic constipation and bloating through Pretreatment Period
Patient is compliant with Interactive voice response System (IVRS)

Exclusion Criteria

Patient has a history of loose or watery stools
Patient has symptoms of or been diagnosed with Irritable Bowel Syndrome (IBS)
Patient has a structural abnormality of the gastrointestinal (GI) tract or a disease or condition that can affect GI motility
Patient has any protocol-excluded or clinically significant medical or surgical history that would limit the patient's ability to complete or participate in this clinical trial or could confound the study assessments

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Linaclotide 290 micrograms	Linaclotide 290 micrograms	Linaclotide 290 micrograms
Placebo	Matching placebo	Matching placebo
Linaclotide 145 Micrograms	Linaclotide 145 micrograms	Linaclotide 145 micrograms

Primary Outcome Measures

Name	Time	Method
9/12 Week Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder	12-week treatment period	A 9/12 Week CSBM 3+1 Responder is a patient who is a CSBM 3+1 Weekly Responder for at least 9 out of the 12 weeks of the Treatment Period. A CSBM 3+1 Weekly Responder is a patient who had a CSBM Weekly Frequency Rate that was 3 or greater and increased by 1 or more from baseline.

Secondary Outcome Measures

Name	Time	Method
9/12 Week Complete Spontaneous Bowel Movement (CSBM) 3+1 Responder	12-week treatment period	A 9/12 Week CSBM 3+1 Responder is a patient who is a CSBM 3+1 Weekly Responder for at least 9 out of the 12 weeks of the Treatment Period. A CSBM 3+1 Weekly Responder is a patient who had a CSBM Weekly Frequency Rate that was 3 or greater and increased by 1 or more from baseline.
Change From Baseline in 12-Week Abdominal Bloating	Baseline and 12-week treatment period	Abdominal Bloating was measured daily using an 11-point Numerical Rating Scale (NRS) where a value of 0 represents no abdominal bloating and a value of 10 represents very severe abdominal bloating. The abdominal bloating score from Baseline is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization up to the time of randomization (Visit 3, Day 1). The change from baseline in 12-Week Abdominal Bloating score is the difference between the average nonmissing daily patient assessments of abdominal bloating scores during the 14 day Baseline period, and the average of the nonmissing daily patient assessments of abdominal bloating scores reported during the 12 week Treatment Period.
Percent Change From Baseline in 12-week Abdominal Bloating	Baseline and 12-week treatment period	Abdominal Bloating was measured daily using an 11-point Numerical Rating Scale (NRS) where a value of 0 represents no abdominal bloating and a value of 10 represents very severe abdominal bloating. The abdominal bloating score from Baseline is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). The percent change from baseline in 12-Week Abdominal Bloating score is the percentage difference between the average nonmissing daily patient assessments score of abdominal bloating scores during the 14 day Baseline period, and the average of the nonmissing daily patient assessments of abdominal bloating scores reported during the 12 week Treatment Period.
Percent Change From Baseline in Abdominal Bloating at Week 12	Baseline and Week 12	Abdominal bloating was measured daily using an 11-point Numerical Rating Scale (NRS) where a value of 0 represents no abdominal bloating and a value of 10 represents very severe abdominal bloating. The abdominal bloating score from Baseline is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). The percent change from baseline at Week 12 in Abdominal Bloating score is the percentage difference between the average nonmissing daily patient assessments of abdominal bloating scores during the 14 day Baseline period, and the average of the nonmissing daily patient assessments of abdominal bloating scores reported during Week 12.
6/12 Week Abdominal Bloating 30% Responder	12-week treatment period	A patient was a 6/12 week abdominal bloating 30% responder if, for at least 6 weeks of the 12-week treatment period, that patient's improvement from baseline in the weekly abdominal bloating score was ≥ 30% from baseline.
Change From Baseline in 12-week CSBM Frequency Rate	Baseline and 12-week treatment period	A patient's 12-week CSBM frequency rate from Baseline is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's 12-week CSBM frequency rate was the CSBM rate (CSBMs/week) calculated over the 12 weeks of the treatment period. Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.
Change From Baseline in CSBM Frequency Rate at Week 1.	Baseline and Week 1	A patient's CSBM frequency rate from Baseline is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's CSBM frequency rate at week 1 was the CSBM rate (CSBMs/week) calculated over that week. Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.
Change From Baseline in CSBM Frequency Rate at Week 4.	Baseline and Week 4	A patient's CSBM frequency rate from Baseline is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's CSBM frequency rate at week 4 was the CSBM rate (CSBMs/week) calculated over that week. Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.
Change From Baseline in CSBM Frequency Rate at Week 8	Baseline and Week 8	A patient's CSBM frequency rate from Baseline is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's CSBM frequency rate at week 8 was the CSBM rate (CSBMs/week) calculated over that week. Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.
Change From Baseline in CSBM Frequency Rate at Week 12	Baseline and Week 12	A patient's CSBM frequency rate from Baseline is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's CSBM frequency rate at week 12 was the CSBM rate (CSBMs/week) calculated over that week. Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.
Change From Baseline in 12-Week SBM Frequency Rate	12-week treatment period	A patient's Baseline SBM frequency rate is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's 12-week SBM frequency rate was the SBM rate (SBMs/week) calculated over the 12 weeks of the treatment period. Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.
Change From Baseline in SBM Frequency Rate at Week 1	Baseline and Week 1	A patient's baseline SBM frequency rate is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's SBM frequency rate at week 1 was the SBM rate (SBMs/week) calculated over that week. Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.
Change From Baseline in SBM Frequency Rate at Week 4	Baseline and Week 4	A patient's baseline SBM frequency rate is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's SBM frequency rate at Week 4 was the SBM rate (SBMs/week) calculated over that week. Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.
Change From Baseline in SBM Frequency Rate at Week 8	Baseline and Week 8	A patient's baseline SBM frequency rate is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's SBM frequency rate at Week 8 was the SBM rate (SBMs/week) calculated over that week. Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.
Change From Baseline in SBM Frequency Rate at Week 12	Baseline and Week 12	A patient's baseline SBM frequency rate is derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's SBM frequency rate at week 12 was the SBM rate (SBMs/week) calculated over that week. Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.
Change From Baseline in the Number of Days With a Spontaneous Bowel Movement (SBM)	Baseline and 12-week treatment period	A patient's baseline number of days with a Spontaneous Bowel Movement (SBM) was calculated as the number of days with at least 1 Spontaneous Bowel Movement (SBM), derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's number of days with a SBM during the Treatment Period was calculated as the number of days with at least 1 Spontaneous Bowel Movement (SBM), divided by treatment duration (in days), and multiplied by 7. Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.
SBM Within 24 Hours After the First Dose of Investigational Product	24 hours from first dose of investigational product (Day 1)	The proportion of patients with a SBM within 24 hours of first taking investigational product in each linaclotide dose group was compared with the proportion in the placebo group using the Cochran-Mantel-Haenszel (CMH) test controlling for geographic region. Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.
Time to Spontaneous Bowel Movement (SBM) After the First Dose of Investigational Product	12-week treatment period	Time to first SBM after the first dose of investigation product was defined as the number of hours between the time of the first dose of investigational product to the occurrence of the first SBM. Patients who did not achieve an SBM were considered censored, with time to censoring defined as the number of hours elapsing from the time of the first dose of investigational product was taken to the end of the day of the last dose, at 12:00 AM (24:00 military time). Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.
Change From Baseline in 12-week Stool Consistency	Baseline and 12-week treatment period	Stool consistency was measured using the 7-point Bristol Stool Form Scale (BSFS): 1. = separate hard lumps like nuts \[difficult to pass\] 2. = sausage shaped but lumpy 3. = like a sausage but with cracks on surface 4. = like a sausage or snake, smooth and soft 5. = soft blobs with clear-cut edges \[passed easily\] 6. = fluffy pieces with ragged edges, a mushy stool 7. = watery, no solid pieces \[entirely liquid\] A patient's BSFS score for the baseline period (14 days before randomization, up to the time of randomization) and for the 12-week treatment period, was the average of the nonmissing BSFS scores from the SBMs reported by the patient during the respective baseline and treatment periods. Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.
Change From Baseline in Stool Consistency at Week 12	Baseline and Week 12	Stool consistency was measured using the 7-point Bristol Stool Form Scale (BSFS): 1. = separate hard lumps like nuts \[difficult to pass\] 2. = sausage shaped but lumpy 3. = like a sausage but with cracks on surface 4. = like a sausage or snake, smooth and soft 5. = soft blobs with clear-cut edges \[passed easily\] 6. = fluffy pieces with ragged edges, a mushy stool 7. = watery, no solid pieces \[entirely liquid\] A patient's BSFS score for the baseline period (14 days before randomization, up to the time of randomization) and at week 12, was the average of the nonmissing BSFS scores from the SBMs reported by the patient during the respective baseline period and during Week 12. Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.
Change From Baseline in 12-week Severity of Straining	Baseline and 12-week treatment period	Severity of straining was measured using a 5-point ordinal scale, where of value of 1 is "not at all" and a value of 5 is "an extreme amount." A patient's straining score for baseline was derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's straining score for the treatment period was the average of the nonmissing straining scores from the SBMs reported by the patient during the 12-week treatment period. Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.
Change From Baseline in Severity of Straining at Week 12	Baseline and Week 12	Severity of straining was measured using a 5-point ordinal scale, where of value of 1 is "not at all" and a value of 5 is "an extreme amount." A patient's straining score for baseline was derived from the Interactive Voice Response System (IVRS) daily diary data collected in the Pretreatment Period, specifically the period of time from 14 days before randomization, up to the time of randomization (Visit 3, Day 1). A patient's straining score at Week 12 was the average of the nonmissing straining scores from the SBMs reported by that patient during analysis Week 12. Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.
9/12 Week Mild Straining and Diarrhea-free Responder	12-week treatment period	A patient was a 9/12 week mild straining and diarrhea-free responder if that patient met the weekly criterion for at least 9 weeks of the 12-week treatment period. A patient was considered to have met the weekly criterion in a given week if that patient had a nonmissing average straining score ≤ 2 (where a value of 1 represents no straining, an a value of 5 represents an extreme amount of straining), and the patient had no diarrhea adverse event (AE) reported for that week. Only the Placebo versus Linaclotide 145 micrograms arm comparison is a secondary measure type for this outcome measure. The additional data for the Linaclotide 290 micrograms arm (a pre-specified additional outcome measure) is presented here for ease of comparison.

Trial Locations

Locations (151): Forest Investigative Site 006
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Boston, Massachusetts, United States
Forest Investigative Site 100
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Houston, Texas, United States
Forest Investigative Site 002
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Miami, Florida, United States
Forest Investigative Site 080
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Las Vegas, Nevada, United States
Forest Investigative Site 120
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Cincinnati, Ohio, United States
Forest Investigative Site 010
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Westlake Village, California, United States
Forest Investigative Site 151
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Santa Monica, California, United States
Forest Investigative Site 117
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Clive, Iowa, United States
Forest Investigative Site 017
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Great Neck, New York, United States
Forest Investigative Site 093
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Albuquerque, New Mexico, United States
Forest Investigative Site 089
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Wilmington, North Carolina, United States
Forest Investigative Site 081
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Levittown, Pennsylvania, United States
Forest Investigative Site 022
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Scottsdale, Arizona, United States
Forest Investigative Site 095
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San Carlos, California, United States
Forest Investigative Site 106
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Anaheim, California, United States
Forest Investigative Site 066
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Mission Hills, California, United States
Forest Investigative Site 047
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Bradenton, Florida, United States
Forest Investigative Site 130
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New Smyrna Beach, Florida, United States
Forest Investigative Site 037
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Stockbridge, Georgia, United States
Forest Investigative Site 143
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Davenport, Iowa, United States
Forest Investigative Site 146
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Clive, Iowa, United States
Forest Investigative Site 128
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Lexington, Kentucky, United States
Forest Investigative Site 134
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Madisonville, Kentucky, United States
Forest Investigative Site 099
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Shreveport, Louisiana, United States
Forest Investigative Site 141
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Jackson, Mississippi, United States
Forest Investigative Site 044
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Brooklyn, New York, United States
Forest Investigative Site 094
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Asheville, North Carolina, United States
Forest Investigative Site 142
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Asheboro, North Carolina, United States
Forest Investigative Site 075
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Boone, North Carolina, United States
Forest Investigative Site 084
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Harrisburg, North Carolina, United States
Forest Investigative Site 039
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Fayetteville, North Carolina, United States
Forest Investigative Site 029
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Greensboro, North Carolina, United States
Forest Investigative Site 078
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Greensboro, North Carolina, United States
Forest Investigative Site 027
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Raleigh, North Carolina, United States
Forest Investigative Site 139
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High Point, North Carolina, United States
Forest Investigative Site 073
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Hickory, North Carolina, United States
Forest Investigative Site 050
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Hickory, North Carolina, United States
Forest Investigative Site 026
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Columbus, Ohio, United States
Forest Investigative Site 056
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Cleveland, Ohio, United States
Forest Investigative Site 098
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Dayton, Ohio, United States
Forest Investigative Site 090
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Dayton, Ohio, United States
Forest Investigative Site 001
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Pittsburgh, Pennsylvania, United States
Forest Investigative Site 085
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Mentor, Ohio, United States
Forest Investigative Site 046
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Simpsonville, South Carolina, United States
Forest Investigative Site 092
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Dakota Dunes, South Dakota, United States
Forest Investigative Site 138
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Kingsport, Tennessee, United States
Forest Investigative Site 125
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Austin, Texas, United States
Forest Investigative Site 067
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Katy, Texas, United States
Forest Investigative Site 005
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Dallas, Texas, United States
Forest Investigative Site 111
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Fort Worth, Texas, United States
Forest Investigative Site 065
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Sugarland, Texas, United States
Forest Investigative Site 053
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Charlottesville, Virginia, United States
Forest Investigative Site 108
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Chesapeake, Virginia, United States
Forest Investigative Site 136
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Chesapeake, Virginia, United States
Forest Investigative Site 054
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Sudbury, Ontario, Canada
Forest Investigative Site 086
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Toronto, Ontario, Canada
Forest Investigative Site 112
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Overland Park, Kansas, United States
Forest Investigative Site 034
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Wichita, Kansas, United States
Forest Investigative Site 028
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Newton, Kansas, United States
Forest Investigative Site 118
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Oklahoma City, Oklahoma, United States
Forest Investigative Site 030
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San Antonio, Texas, United States
Forest Investigative Site 076
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San Antonio, Texas, United States
Forest Investigative Site 105
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Salt Lake City, Utah, United States
Forest Investigative Site 148
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Christiansburg, Virginia, United States
Forest Investigative Site 051
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Ft. Myers, Florida, United States
Forest Investigative Site 145
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Traverse City, Michigan, United States
Forest Investigative Site 152
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Vaughan, Ontario, Canada
Forest Investigative Site 070
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Chesterfield, Michigan, United States
Forest Investigative Site 014
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Hagerstown, Maryland, United States
Forest Investigative Site 124
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Metairie, Louisiana, United States
Forest Investigative Site 088
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Marlton, New Jersey, United States
Forest Investigative Site 033
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Vineland, New Jersey, United States
Forest Investigative Site 077
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Fremont, Nebraska, United States
Forest Investigative Site 113
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Sandy, Utah, United States
Forest Investigative Site 082
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La Crosse, Wisconsin, United States
Forest Investigative Site 059
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Sarnia, Ontario, Canada
Forest Investigative Site 019
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Ogden, Utah, United States
Forest Investigative Site 079
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Tucson, Arizona, United States
Forest Investigative Site 129
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Chattanooga, Tennessee, United States
Forest Investigative Site 008
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Chevy Chase, Maryland, United States
Forest Investigative Site 058
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Shreveport, Louisiana, United States
Forest Investigative Site 147
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Toronto, Ontario, Canada
Forest Investigative Site 116
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Greer, South Carolina, United States
Forest Investigative Site 024
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Towson, Maryland, United States
Forest Investigative Site 063
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Albuquerque, New Mexico, United States
Forest Investigative Site 052
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Henderson, Nevada, United States
Forest Investigative Site 036
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Clifton, New Jersey, United States
Forest Investigative Site 119
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Statesville, North Carolina, United States
Forest Investigative Site 140
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Davidson, North Carolina, United States
Forest Investigative Site 031
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Greensboro, North Carolina, United States
Forest Investigative Site 025
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Cincinnati, Ohio, United States
Forest Investigative Site 068
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Wadsworth, Ohio, United States
Forest Investigative Site 110
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Reading, Pennsylvania, United States
Forest Investigative Site 035
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Dallas, Texas, United States
Forest Investigative Site 049
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Pasadena, Texas, United States
Forest Investigative Site 072
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Lynchburg, Virginia, United States
Forest Investigative Site 069
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Newport News, Virginia, United States
Forest Investigative Site 013
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Norfolk, Virginia, United States
Forest Investigative Site 018
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Phoenix, Arizona, United States
Forest Investigative Site 149
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Glendale, Arizona, United States
Forest Investigative Site 021
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Marietta, Georgia, United States
Forest Investigative Site 009
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San Diego, California, United States
Forest Investigative Site 071
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Tucson, Arizona, United States
Forest Investigative Site 091
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Boynton Beach, Florida, United States
Forest Investigative Site 020
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Chandler, Arizona, United States
Forest Investigative Site 061
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Phoenix, Arizona, United States
Forest Investigative Site 102
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Chandler, Arizona, United States
Forest Investigative Site 126
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Goodyear, Arizona, United States
Forest Investigative Site 135
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North Little Rock, Arkansas, United States
Forest Investigative Site 012
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Boulder, Colorado, United States
Forest Investigative Site 104
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Laguna Hills, California, United States
Forest Investigative Site 060
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Longmont, Colorado, United States
Forest Investigative Site 042
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Brooksville, Florida, United States
Forest Investigative Site 114
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Jacksonville, Florida, United States
Forest Investigative Site 041
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Colorado Springs, Colorado, United States
Forest Investigative Site 007
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Bristol, Connecticut, United States
Forest Investigative Site 133
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Coral Gables, Florida, United States
Forest Investigative Site 097
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Lauderdale Lakes, Florida, United States
Forest Investigative Site 045
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Colorado Springs, Colorado, United States
Forest Investigative Site 016
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Kissimmee, Florida, United States
Forest Investigative Site 011
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Marietta, Georgia, United States
Forest Investigative Site 083
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Orlando, Florida, United States
Forest Investigative Site 153
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Waterbury, Connecticut, United States
Forest Investigative Site 004
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Jupiter, Florida, United States
Forest Investigative Site 132
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Port Orange, Florida, United States
Forest Investigative Site 023
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Woodstock, Georgia, United States
Forest Investigative Site 003
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Miami, Florida, United States
Forest Investigative Site 040
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Ocala, Florida, United States
Forest Investigative Site 087
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St. Petersburg, Florida, United States
Forest Investigative Site 115
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Zephyrhills, Florida, United States
Forest Investigative Site 122
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Peoria, Illinois, United States
Forest Investigative Site 127
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Seminole, Florida, United States
Forest Investigative Site 109
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Sandy Springs, Georgia, United States
Forest Investigative Site 015
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Idaho Falls, Idaho, United States
Forest Investigative Site 043
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Rockford, Illinois, United States
Forest Investigative Site 107
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Anderson, Indiana, United States
Forest Investigative Site 055
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Iowa City, Iowa, United States
Forest Investigative Site 101
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Monroe, Louisiana, United States
Forest Investigative Site 062
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Baltimore, Maryland, United States
Forest Investigative Site 121
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Baton Rouge, Louisiana, United States
Forest Investigative Site 032
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Wichita, Kansas, United States
Forest Investigative Site 064
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Tampa, Florida, United States
Forest Investigative Site 048
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Omaha, Nebraska, United States
Forest Investigative Site 123
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Chapel Hill, North Carolina, United States
Forest Investigative Site 074
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Winston-Salem, North Carolina, United States
Forest Investigative Site 096
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Milwaukee, Wisconsin, United States
Forest Investigative Site 038
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Richmond, Virginia, United States
Forest Investigative Site 131
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DeLand, Florida, United States
Forest Investigative Site 150
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Oviedo, Florida, United States
Forest Investigative Site 137
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Inverness, Florida, United States
Forest Investigative Site 103
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Spokane, Washington, United States