MedPath

PF-06372865 In Subjects With Chronic Low Back Pain

Phase 2
Completed
Conditions
Chronic Low Back Pain
Interventions
Drug: PF-06372865
Drug: Placebo
Drug: Naproxen
Registration Number
NCT02262754
Lead Sponsor
Pfizer
Brief Summary

PF-06372865 In Subjects With Chronic Low Back Pain

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
302
Inclusion Criteria
Read More
Exclusion Criteria
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PF-06372865PF-06372865Daily BID dosing for 4 weeks
PlaceboPlaceboDaily BID dosing for 4 weeks
NaproxenNaproxenDaily BID dosing for 4 weeks
Primary Outcome Measures
NameTimeMethod
Number of Participants With Laboratory AbnormalitiesBaseline up to 28 days after the last dose of study treatment (Day 56)

Abnormality criteria included: hemoglobin, hematocrit and red blood cells (RBCs) (less than \[\<\] 0.8\*lower limit of normal \[LLN\]); white blood cells (WBC) (\<0.6\*LLN, greater than \[\>\] 1.5\*upper limit of normal \[ULN\]); MCV, MCH, MCHC (\<0.9\*LLN, \>1.1\*ULN); platelets (\<0.5\*LLN\>, \>1.75\*ULN); neutrophils, lymphocytes(\<0.8\*LLN, \>1.2\*ULN); eosinophils, basophils, monocytes (\>1.2\*ULN); total bilirubin (\>1.5\*ULN); aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase (\>3\*ULN); total protein, albumin (\<0.8\*LLN, \>1.2\*ULN); creatinine, blood urea nitrogen (\>1.3\*ULN); glucose (\<0.6\*LLN, \>1.5\*ULN); uric acid (\>1.2\*ULN); sodium, potassium, chloride, calcium, bicarbonate (\<0.9\*LLN, \>1.1\*ULN); urine pH (\<4.5, \>8); qualitative urine glucose, ketones, protein, blood values (greater than or equal to \[\>=\] 1) in urine dipstick test; urine RBC, WBC (\>=20); hyaline casts (\>1), bacteria (\>20).

Number of Participants With Vital Sign AbnormalitiesBaseline up to Follow-up (44 days)

Participants who met the criteria for abnormal findings in vital signs data were reported. Criteria for abnormalities in vital signs: supine systolic blood pressure (SBP) \<90 millimeter of mercury (mmHg), supine diastolic BP (DBP) \<50 mmHg, supine pulse rate \<40 beats per minute (bpm) or \>120 bpm. Maximum increase or decrease from baseline in supine SBP \>=30 mmHg and maximum increase or decrease from baseline in supine DBP \>=20 mmHg.

Number of Participants With Categorical Scores on the Columbia Suicide Severity Rating Scale (C-SSRS)Screening, Baseline, Week 1, 2, 3, 4

The C-SSRS (mapped to Columbia Classification Algorithm of Suicide Assessment \[C-CASA\]) is an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced following: completed suicide =1, suicide attempt =2 (response of "Yes" on "actual attempt"), preparatory acts toward imminent suicidal behavior =3 ("Yes" on "preparatory acts or behavior"), suicidal ideation =4 ("Yes" on "wish to be dead", "non-specific active suicidal thoughts", "active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent), any suicidal behavior or ideation, self-injurious behavior =7 ("Yes" on "Has participant engaged in non-suicidal self-injurious behavior").

Change From End of Treatment Visit in Physician's Withdrawal Checklist (PWC) Score at Follow-up VisitEnd of treatment (Day 30), follow-up (Day 44)

PWC is a 20 item physician rated interview to measure anxiolytic drug withdrawal-related signs and symptoms. Each individual item score ranges from 0 (not present) to 3 (severe), where higher scores = more affected condition. PWC total score range from 0 (not present) to 60 (severe), where higher score = more affected condition. Change: score at follow-up visit minus score at the end of treatment visit.

Change From Baseline in Daily Low Back Pain Intensity (LBPI) Score as Measured by an 11-point Numeric Rating Scale (NRS) at Week 4Baseline, Week 4

Daily average low back pain was assessed on an 11-point numeric rating scale (NRS). Participants described their average low back pain during the past 24 hours on a scale ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicate higher pain. Baseline value was calculated as the mean of the scores over the last 7 days in the placebo run-in period, prior to randomization. Post-baseline weekly scores were calculated based on the mean of the scores over the 7 days prior to and including the day at the end of the corresponding week.

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)Baseline up to 28 days after the last dose of study treatment (Day 56)

An AE was any untoward medical occurrence in a participant who received study treatment without regard to possibility of causal relationship. The SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability or incapacity, congenital anomaly. Treatment-emergent are events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pretreatment state. AEs included both serious and non-serious adverse events.

Number of Participants With Electrocardiogram (ECG) AbnormalitiesBaseline up to Follow-up (44 days)

Participants with abnormal ECG findings were reported. Criteria for potential clinical concern in ECG parameters: maximum (max.) PR interval of \>=300 milliseconds (msec), maximum QRS interval \>=140 msec, maximum QTCF interval (Fridericia's Correction) of 450 to \<480 msec, 480 to \<500 msec and \>=500 msec, maximum of \>=25 percent (%) increase from baseline (IFB) value of \>200 msec and \>=50% for baseline value of less than or equal to (\<=) 200 msec for PR interval, maximum increase from baseline of \>=50% for QRS interval, maximum increase from baseline of \>=30 msec to \<60 msec and maximum increase from baseline of \>60 msec in QTCF interval (Fridericia's Correction).

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Daily Low Back Pain Intensity (LBPI) as Measured by an 11-point Numeric Rating Scale (NRS) at Week 1, 2 3 and 4Baseline, Week 1, 2, 3, 4

Average back pain was assessed with an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Participants described their average low back pain during the past 24 hours by choosing the appropriate number from 0 to 10.

Percent Change From Baseline in Daily Low Back Pain Intensity (LBPI) as Measured by an 11-point Numeric Rating Scale (NRS) at Week 1, 2, 3 and 4Baseline, Week 1, 2, 3, 4

Average back pain was assessed with an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Participants described their average low back pain during the past 24 hours by choosing the appropriate number from 0 to 10.

Number of Participants With Sustained Response Rates in Daily Average LBPI NRS Scores at Greater Than or Equal to (>=) 30 Percent and >=50 Percent Reduction From BaselineBaseline up to Week 4

Average back pain was assessed with an 11-point NRS ranging from 0 (no pain) to 10 (worst possible pain), where higher scores indicated higher pain. Participants described their average low back pain during the past 24 hours by choosing the appropriate number from 0 to 10. Percentage of reduction from baseline in the daily average LBPI NRS score was calculated as: (\[daily value - baseline value\] divided by baseline value) multiplied by 100. Number of participants with sustained response rates (for a minimum of 4 consecutive days) in the daily average LBPI NRS scores that were at \>=30 percent and \>=50 percent reduced from baseline were reported.

Number of Participants Withdrawn Due to Lack of EfficacyBaseline up to Week 4

Participants withdrew from the study due to lack of efficacy (insufficient clinical response) were reported.

Time to Withdrawal Due to Lack of EfficacyBaseline up to Week 4

Kaplan Meier and Cox Proportional Hazards analyses were to be used to compute the time to withdrawal due to lack of efficacy. Withdrawal due to lack of efficacy was identified from the participant summary case report form (CRF) page and where reason was identified as "Insufficient Clinical Response". Time to withdrawal was calculated as Date of withdrawal - Date of Randomization.

Number of Participants Using Rescue MedicationWeek 1, 2, 3, 4

Participants were permitted to use any commercial product (tablet/caplet/capsule) of acetaminophen (paracetamol) 500 mg as a rescue medication. Number of participants who used rescue medication were reported.

Number of Days Participants Used the Rescue MedicationWeek 1, 2, 3, 4

The number of days for which the participants used the rescue medication were reported. Participants recorded the usage of acetaminophen rescue medication in the daily diary.

Amount of Rescue Medication Used by the ParticipantsWeek 1, 2, 3, 4

The amount of rescue medication (Acetaminophen \[paracetamol\]) used was reported. Participants were permitted to use any commercial product of acetaminophen tablet/caplet/capsule.

Change From Baseline in Roland-Morris Disability Questionnaire (RMDQ) Total Score at Week 1, 2, and 3Baseline, Week 1, 2, 3

Each participant assessed his or her own disability due to low back pain using the RMDQ worksheet. The RMDQ total score was calculated as the total number of statements that were checked; the RMDQ total possible scores ranges from 0 to 24, with higher scores indicating greater disability.

Change From Baseline in Roland-Morris Disability Questionnaire (RMDQ) Total Score at Week 4Baseline, Week 4

Each participant assessed his or her own disability due to low back pain using the RMDQ worksheet. The RMDQ total score was calculated as the total number of statements that were checked; the RMDQ total possible scores ranges from 0 to 24, with higher scores indicating greater disability.

Change From Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) at Week 2 and 4Baseline, Week 2, Week 4

This test assesses verbal learning and memory. Participants are given a list of 12 words and asked to repeat as many words as they can recall during 3 separate learning trials. The total recall score ranges from 0 (no memory) to 36 (best memory) while the delayed recall trial score ranges from 0 (no memory) to 12 (best memory); higher scores indicated greater verbal learning and recall.

Chronic Low Back Pain (CLBP) Responder Index AnalysisWeek 1, 2, 3, 4

Participants were successful responders if they had any of the following: \>=30 percent reduction in mean daily average LBPI from baseline to particular week; decrease of \>=30 percent in participant's global assessment of low back pain (disease activity) from baseline to particular week or no worsening (increase) in RMDQ total score from baseline to particular week.

Change From Baseline in Participant's Global Assessment (PtGA) of Low Back Pain Score at Week 1, 2, 3 and 4Baseline, Week 1, 2, 3, 4

Participant rated 5-point Likert scale ranging from 0 (no pain) to 4 (worst possible pain) with a higher score indicating greater level of pain.

Patient Global Impression of Change (PGI-C) ScoreWeek 1, 2, 3, 4

PGI-C was a participant rated instrument to measure participant's assessment of change in his or her overall status since the previous visit on a 7-point scale; ranging from 1 (very much improved) to 7 (very much worse), where higher scores indicated more worsening.

Number of Participants With Global Evaluation of Study Medication (GESM) at Week 4Week 4

Participants rated their study treatment by GESM questionnaire. It was a qualitative measure of efficacy utilizing a 4-point Likert scale ranging from 1 (poor) to 4 (excellent), where higher score indicated a better overall response to the treatment. Number of participants who reported a particular score had been reported.

Plasma Concentration of PF-06372865Baseline, Week 1, 2, 3, 4

Data was calculated by setting concentration values below the lower limit of quantification (LLOQ) to zero. The LLOQ was \<0.0100 nanogram per milliliter (ng/mL).

Plasma Concentration of NaproxenBaseline, Week 1, 2, 3, 4

Data was calculated by setting concentration values below the LLOQ to zero. The LLOQ was \<1000 ng/mL.

Trial Locations

Locations (45)

S&W Clinical Research

🇺🇸

Fort Lauderdale, Florida, United States

Neuro-Pain Medical Center

🇺🇸

Fresno, California, United States

Pines Clinical Research Inc.

🇺🇸

Pembroke Pines, Florida, United States

National Clinical Research - Norfolk, Inc.

🇺🇸

Norfolk, Virginia, United States

River Birch Research Alliance, LLC

🇺🇸

Blue Ridge, Georgia, United States

Florida Research Network, LLC

🇺🇸

Gainesville, Florida, United States

Avail Clinical Research, LLC

🇺🇸

DeLand, Florida, United States

Broward Research Group

🇺🇸

Hollywood, Florida, United States

Chicago Anesthesia Associates

🇺🇸

Chicago, Illinois, United States

Columbus Regional Research Institute

🇺🇸

Columbus, Georgia, United States

Better Health Clinical Research, Inc./Georgia Pain & Spine Care, Inc.

🇺🇸

Newnan, Georgia, United States

Southeast Regional Research Group

🇺🇸

Savannah, Georgia, United States

Family Medicine center

🇺🇸

Columbus, Georgia, United States

Accord Clinical Research, LLC

🇺🇸

Port Orange, Florida, United States

CRC of Jackson

🇺🇸

Jackson, Mississippi, United States

Physician's Surgery Center

🇺🇸

Jackson, Mississippi, United States

North Georgia Internal medicine

🇺🇸

Woodstock, Georgia, United States

Clinical Trial Network

🇺🇸

Houston, Texas, United States

Summit Research Network (Seattle) LLC

🇺🇸

Seattle, Washington, United States

Arizona Research Center, Inc.

🇺🇸

Phoenix, Arizona, United States

Lee Medical Associates, PA

🇺🇸

San Antonio, Texas, United States

Arthritis & Rheumatic Care Center

🇺🇸

South Miami, Florida, United States

Agave Clinical Research, LLC

🇺🇸

Mesa, Arizona, United States

Global Research

🇺🇸

Anaheim, California, United States

Providence Clinical Research

🇺🇸

North Hollywood, California, United States

Elite Clinical Trials, Incorporate

🇺🇸

Wildomar, California, United States

Stamford Therapeutics Consortium

🇺🇸

Stamford, Connecticut, United States

Jacksonville Center for Clinical Research

🇺🇸

Jacksonville, Florida, United States

Miami Research Associates

🇺🇸

South Miami, Florida, United States

Better Health Clinical Research, Inc.

🇺🇸

Newnan, Georgia, United States

Drug Studies America

🇺🇸

Marietta, Georgia, United States

North Georgia Clinical Research

🇺🇸

Woodstock, Georgia, United States

Centex Studies, Inc

🇺🇸

Lake Charles, Louisiana, United States

Wake Research Associates, LLC

🇺🇸

Raleigh, North Carolina, United States

Omega Medical Research

🇺🇸

Warwick, Rhode Island, United States

Boston Clinical Trials

🇺🇸

Boston, Massachusetts, United States

Wake Internal Medicine Consultants, Inc.

🇺🇸

Raleigh, North Carolina, United States

AAIR Research Center

🇺🇸

Rochester, New York, United States

Drug Trials America

🇺🇸

Hartsdale, New York, United States

Progressive Clinical Research

🇺🇸

San Antonio, Texas, United States

ActivMed Practices & Research, Inc.

🇺🇸

Methuen, Massachusetts, United States

Altoona Center for Clinical Research

🇺🇸

Duncansville, Pennsylvania, United States

Compass Research, LLC

🇺🇸

Orlando, Florida, United States

The Center for Clinical Research

🇺🇸

Winston-Salem, North Carolina, United States

Summit Research Network (Oregon), Inc.

🇺🇸

Portland, Oregon, United States

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