Single-Agent Glasdegib In Patients With Myelofibrosis Previously Treated With Ruxolitinib
- Conditions
- Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis
- Interventions
- Drug: Placebo
- Registration Number
- NCT02226172
- Lead Sponsor
- Pfizer
- Brief Summary
A lead-in cohort of \~20 patients with primary or secondary myelofibrosis previously treated with 1 or more Janus kinase inhibitors enrolled to single-agent glasdegib to evaluate safety and tolerability. Following the lead-in, a phase 2, double blind, 2-arm study, randomized 2:1 to oral single-agent glasdegib versus placebo in 201 patients resistant or intolerant to ruxolitinib.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 21
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Arm B Placebo Oral daily dose of placebo 100 mg tablet in a continuous regimen of 28-day cycles. Arm A Glasdegib (PF-04449913) Oral daily dose of glasdegib (PF-04449913) 100 mg tablet in a continuous regimen of 28-day cycles.
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving Spleen Volume Reduction (SVR) ≥35% as Measured by Magnetic Resonance Imaging (MRI)/Computed Tomography (CT) Scan at Week 24 in the Randomized Cohort Week 24 The double blind, randomized, placebo controlled phase of the study was not enrolled after the study was terminated early so no data were collected to assess this endpoint.
Number of Participants With Treatment Emergent Treatment -Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Lead-in Cohort Baseline up to Week 131 Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. 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/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 28 days after last dose of study drug (up to Week 131) that were absent before treatment or that worsened relative to pre-treatment state. Relatedness to study drug was assessed by the investigator. AEs included both serious and non-serious adverse event.
Number of Participants With Treatment -Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Lead-in Cohort Baseline up to Week 131 An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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/incapacity; congenital anomaly. Treatment-emergent were events between first dose of study drug and up to 28 days after last dose of study drug (up to Week 131) 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 Treatment Emergent Adverse Events (AEs) According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03: Lead-in Cohort Baseline up to Week 131 AE was untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. SAE was AE resulting in any outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience; persistent or significant disability; congenital anomaly.Treatment-emergent were events between first dose of study drug and up to 28 days after last dose of study drug (up to Week 131) that were absent before treatment or that worsened relative to pretreatment state.AE were assessed according to maximum severity grading based on NCI CTCAE Version 4.03.Grade 1=mild; Grade 2=moderate; within normal limits. Grade 3=severe or medically significant but not immediately life-threatening; Grade 4=life-threatening or disabling; urgent intervention indicated; Grade 5=death. Only categories with at least 1 participant with event were reported.
Number of Participants With Laboratory Test Abnormalities According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 Grade 3 and Above Chemistry Test Abnormalities: Lead-in Cohort Baseline up to Week 131 ALT/AST g1:\>ULN 3\*ULN, g2:\>3-5\*ULN, g3:\>5 20\*ULN, g4:\>20\*ULN); Alkaline Phosphatase (g1:\>ULN 2.5\*ULN,g2:\>2.5-5\*ULN, g3:\>5 20\*ULN, g4:\>20\*ULN); Creatinine (g1:\>ULN-1.5\*ULN,g2:\>1.5-3\*ULN, g3:\>3 6\*ULN, g4:\>6\*ULN);hyperglycemia (g1:\>ULN-160,g2:\>160 250, g3:\>250 500, g4:\>500mg/dL);bilirubin(total) (g1:\>ULN-1.5\*ULN, g2:\>1.5-3\*ULN, g3:\>3 10\*ULN,g4:\>10\*ULN);hypoglycaemia (g1:\<LLN-55,g2:\<55-40, g3:\<40 30,g4:\<30mg/dL); hyperkalemia (g1:\>ULN-5.5,g2:\>5.5-6, g3:\>6 7,g4:\>7mmol/L);hypokalemia (g1:\<LLN-3,g2:\<LLN-3, g3:\<3 2.5, g4:\<2.5mmol/L);hypermagnesemia (g1:\>ULN-3,g3:\>3 8, g4:\>8mg/dL);hypocalcemia (g1:\<LLN-8,g2:\<8-7, g3:\<7-6, g4:\<6mg/dL); hypercalcemia (g1:\>ULN-11.5,g2:\>11.5-12.5, g3:\>12.5-13.5, g4:\>13.5mg/dL); hypomagnesemia (g1:\<LLN-1.2,g2:\<1.2-0.9,g3:\<0.9-0.7, g4:\<0.7mg/dL); hyponatremia (g1:\<LLN-130,g3:\<130-120, g4:\<120mmol/L);hypoalbuminemia (g1:\<LLN-3,g2:\<3 2,g3:\<2, g4:lifethreatening);hypophosphatemia (g1:\<LLN-2.5,g2:\<2.5-2, g3:\<2-1, g4:\<1mg/dL).
Number of Participants With Laboratory Abnormalities: Lead-in Cohort Baseline up to Week 131 Abnormality: hematology: hemoglobin less than (\<)0.8\*lower limit of normal(LLN), platelets \<0.5\*LLN greater than (\>)1.75\*upper limit of normal(ULN), white blood cell count(WBC) \<0.6\* LLN \>1.5\* ULN,lymphocytes, total neutrophils\<0.8\* LLN \>1.2\* ULN, band Cells, basophils, eosinophils, monocytes \>1.2\*ULN, blast cells \>1.0\*ULN. Coagulation: activated partial thromboplastin time, prothrombin international ratio \>1.1\* ULN. Liver function: bilirubin \>1.5\*ULN, AST, ALT,lactate dehydrogenase,alkaline phosphatase \>3.0\*ULN, protein,albumin \<0.8\* LLN \>1.2\* ULN. Renal:blood urea nitrogen,creatinine \>1.3\*ULN,uric acid \>1.2\*ULN.Electrolytes: sodium \<0.95\*LLN \>1.05\*ULN, potassium, chloride, calcium, magnesium \<0.9\* LLN \>1.1\*ULN,phosphate \<0.8\* LLN \>1.2\* ULN.Chemistry: glucose \<0.6\*LLN \>1.5\*ULN,creatine kinase \>2.0\*ULN, amylase,lipase \>1.5\*ULN.Urinalysis: protein, blood \>1.0\*ULN,red blood cells,WBC \>=20,epithelial cells \>=6,casts,granular casts,hyaline \>1,cellular casts,crystals\>=1,bacteria \>20.
Number of Participants With Laboratory Test Abnormalities According to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 Grade 3 and Above Hematological Test Abnormalities: Lead-in Cohort Baseline up to Week 131 Anemia (grade \[g\]1:\< LLN to 10 gram per deciliter \[g/dL\],g2:\<10 to 8g/dL,g3:\<8g/dL, g4:lifethreatening); platelet (g1:\<LLN to 75\*10\^3/millimeter\[mm\]\^3, g2:\<75\*10\^3/mm\^3 to 50\*10\^3/mm\^3, g3:\<50\*10\^3/mm\^3 to 25\*10\^3/mm\^3, g4:\<25\*10\^3/mm\^3); lymphopenia (g1:\<LLN to 8\*10\^2/mm\^3, g2:\<8\*10\^2 to 5\*10\^2/mm\^3, g3:\<5\*10\^2 to 2\*10\^2/mm\^3, g4:\<2\*10\^2/mm\^3);neutrophil (Absolute) (g1:\<LLN to 15\*10\^2/mm\^3, g2:\<15\*10\^2 to 10\*10\^2/mm\^3, g3:\<10\*10\^2 to 5\*10\^2/mm\^3, g4:\<5\*10\^2/mm\^3); white blood cell count(g1:\<LLN to 3\*10\^3/mm\^3, g2:\<3\*10\^3 to 2\*10\^3/mm\^3, g3:\<2\*10\^3 to 1\*10\^3/mm\^3, g4:\<1\*10\^3/mm\^3); hemoglobin (g1:increase in hemoglobin level \>0 to 2 g/dL above ULN or above baseline if baseline is above ULN, g2:increase in hemoglobin level\>2 to 4g/dL above ULN or above baseline if baseline is above ULN,g3: increase in hemoglobin level\>4 g/dL above ULN or above baseline if baseline is above ULN).
- Secondary Outcome Measures
Name Time Method Maximum Observed Glasdegib Plasma Concentration (Cmax), Minimum Glasdegib Plasma Concentration Observed Prior to the Next Dose (Cmin), and Average Observed Glasdegib Plasma Concentration (Cavg) in the Lead-in Cohort Cycle 1, Day 15 Cmax was the highest plasma concentration of glasdegib observed directly from the plasma concentration data. Cmin was the lowest plasma concentration of glasdegib observed directly from the plasma concentration data. Cavg was the average concentration at steady state estimated using non-compartmental pharmacokinetic (PK) analysis.
Percentage of Participants Achieving Anemia Response (Transfusion Dependent Versus Independent) in the Randomized Cohort Baseline to end of treatment The double blind, randomized, placebo controlled phase of the study was not enrolled after the study was terminated early so no data were collected to assess this endpoint.
Participant Reported Outcomes of Health Related Quality of Life and Health Status in the Randomised Cohort Baseline to end of treatment The double blind, randomized, placebo controlled phase of the study was not enrolled after the study was terminated early so no data were collected to assess this endpoint.
Number of Participants With Treatment Emergent Treatment -Related Adverse Events (AEs) and Serious Adverse Events (SAEs): Randomized Cohort Baseline up to Week 131 Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. 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/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. Relatedness to study drug was assessed by the investigator.
Number of Participants With Laboratory Abnormalities: Randomized Cohort Baseline up to Week 131 Abnormality: hematology: hemoglobin less than (\<)0.8\*lower limit of normal(LLN), platelets \<0.5\*LLN \>1.75\*upper limit of normal(ULN), white blood cell count(WBC) \<0.6\* LLN greater than (\>)1.5\* ULN,lymphocytes, total neutrophils\<0.8\* LLN \>1.2\* ULN, band Cells, basophils, eosinophils, monocytes \>1.2\*ULN, blast cells \>1.0\*ULN. Coagulation: activated partial thromboplastin time, prothrombin international ratio \>1.1\* ULN. Liver function: bilirubin \>1.5\*ULN, AST, ALT,lactate dehydrogenase,alkaline phosphatase \>3.0\*ULN, protein,albumin \<0.8\* LLN \>1.2\* ULN. Renal:blood urea nitrogen,creatinine \>1.3\* ULN,uric acid \>1.2\* ULN.Electrolytes: sodium \<0.95\*LLN \>1.05\*ULN, potassium, chloride, calcium, magnesium \<0.9\* LLN \>1.1\*ULN,phosphate \<0.8\* LLN \>1.2\* ULN.Chemistry: glucose \<0.6\*LLN \>1.5\*ULN,creatine kinase \>2.0\*ULN, amylase,lipase \>1.5\*ULN.Urinalysis: protein, blood \>1.0\*ULN,red blood cells,WBC \>=20,epithelial cells \>=6,casts,granular casts,hyaline \>1,cellular casts,crystals\>=1,bacteria \>20.
Percentage of Participants Achieving ≥50% Reduction From Baseline in Total Symptom Score (TSS) as Measured by the Myeloproliferative Neoplasm-Symptom Assessment Diary (MPN-SAD) at Week 24 in the Lead-in Cohort Week 24 The MPN-SAD assessed the impact of 9 myelofibrosis symptoms, at their worst, over the past 7 days and over the past 24 hours on a scale of 0 (absent) to 10 (worst imaginable). The 9 symptoms are early satiety, abdominal discomfort, inactivity, night sweats, pruritus, bone pain, pain below the ribs on the left-hand side, fatigue and shortness of breath. The TSS is the sum of the individual scores, excluding inactivity and shortness of breath. The TSS at Week 24 is the average of the daily total scores from the last 28 days of symptom scores immediately prior to Week 24. A higher score indicates worse symptoms.
Monthly Mean Change From Baseline in Overall Total Symptom Score (TSS) in the Lead-in Cohort Weeks 12, 24, 36 and 48 The MPN-SAD assessed the impact of 9 myelofibrosis symptoms, at their worst, over the past 7 days and over the past 24 hours on a scale of 0 (absent) to 10 (worst imaginable). The 9 symptoms are early satiety, abdominal discomfort, inactivity, night sweats, pruritus, bone pain, pain below the ribs on the left-hand side, fatigue and shortness of breath. The TSS is the sum of the individual scores, excluding inactivity and shortness of breath. The TSS at Week 24 is the average of the daily total scores from the last 28 days of symptom scores immediately prior to Week 24. A higher score indicates worse symptoms.
Area Under the Glasdegib Plasma Concentration Versus Time Profile at the End of a Dosing Interval (AUCtau) in the Lead-in Cohort Cycle 1, Day 15 AUCtau was the area under the glasdegib plasma concentration-time profile from time zero to the end of the dosing interval (24 hours) estimated by non-compartmental PK analysis using the linear/log trapezoidal method.
Time to Reach Cmax (Tmax) in the Lead-in Cohort Cycle 1, Day 15 Tmax was the time of the first occurrence of Cmax observed directly from the plasma concentration data.
Monthly Mean Change From Baseline in Overall TSS in the Randomized Cohort Weeks 12, 24, 36 and 48 The double blind, randomized, placebo controlled phase of the study was not enrolled after the study was terminated early so no data were collected to assess this endpoint.
Percentage of Participants Achieving SVR ≥35% as Measured by Magnetic Resonance Imaging/Computed Tomography Scan at Week 24 in the Lead-in Cohort Week 24 MRI (CT scan may have been permitted if MRI was contraindicated) of the spleen and the liver was performed at baseline, then every 12 weeks while the participant was on treatment. The same method of assessment used at baseline was used for the duration of the trial to ensure consistency. Spleen volume was assessed by a central, independent blinded reader.
Percentage of Participants Achieving Anemia Response (Transfusion Dependent Versus Independent) in the Lead-in Cohort Baseline to end of treatment Anemia response was defined as transfusion-independent participants with a ≥20 gram per liter (g/L) increase in hemoglobin (Hb) level where baseline Hb level was \<100 g/L, or baseline transfusion-dependent patients becoming transfusion-independent post-baseline. Transfusion dependency before the start of study treatment was defined as transfusions of ≥6 units of packed red blood cells in the 12 weeks prior to start of study treatment, for a final pre-treatment Hb of \<85 g/L. In addition, the most recent transfusion episode must have occurred in the 28 days prior to study enrollment. Response in transfusion-dependent patients required absence of any packed red blood cell transfusions during any consecutive rolling 12-week interval during the treatment phase, capped by a Hb level of ≥85 g/L.
Median Duration of SVR in the Randomized Cohort Baseline to end of treatment The double blind, randomized, placebo controlled phase of the study was not enrolled after the study was terminated early so no data were collected to assess this endpoint.
Number of Participants With Laboratory Test Abnormalities By Maximum Severity: National Cancer Institute Common Terminology Criteria for Adverse Event (Version 4.0) Grade 3 and Above Hematological Test Abnormalities: Randomized Cohort Baseline up to Week 131 Anemia g1:\< LLN to 10 g/dL, g2:\<10 to 8g/dL, g3:\<8g/dL, g4:lifethreatening); platelet (g1:\<LLN to 75\*10\^3/mm\^3, g2:\<75\*10\^3/mm\^3 to 50\*10\^3/mm\^3, g3:\<50\*10\^3/mm\^3 to 25\*10\^3/mm\^3, g4:\<25\*10\^3/mm\^3); lymphopenia (g1:\<LLN to 8\*10\^2/mm\^3, g2:\<8\*10\^2 to 5\*10\^2/mm\^3, g3:\<5\*10\^2 to 2\*10\^2/mm\^3, g4:\<2\*10\^2/mm\^3);neutrophil (absolute) (g1:\<LLN to 15\*10\^2/mm\^3, g2:\<15\*10\^2 to 10\*10\^2/mm\^3, g3:\<10\*10\^2 to 5\*10\^2/mm\^3, g4:\<5\*10\^2/mm\^3); white blood cell count (g1:\<LLN to 3\*10\^3/mm\^3, g2:\<3\*10\^3 to 2\*10\^3/mm\^3, g3: \<2\*10\^3 to 1\*10\^3/mm\^3, g4:\<1\*10\^3/mm\^3); hemoglobin(g1:increase in hemoglobin level\>0 to 2 g/dL above ULN or above baseline if baseline is above ULN, g2: increase in hemoglobin level\>2 to 4g/dL above ULN or above baseline if baseline is above ULN, g3:increase in hemoglobin level\>4 g/dL above ULN or above baseline if baseline is above ULN).
Number of Participants With Laboratory Test Abnormalities By Maximum Severity: National Cancer Institute Common Terminology Criteria for Adverse Event (Version 4.0) Grade 3 and Above Chemistry Test Abnormalities: Randomized Cohort Baseline up to Week 131 ALT/AST g1:\>ULN 3\*ULN, g2:\>3-5\*ULN, g3:\>5 20\*ULN, g4:\>20\*ULN); Alkaline Phosphatase (g1:\>ULN 2.5\*ULN, g2:\>2.5-5\*ULN, g3:\>5 20\*ULN, g4:\>20\*ULN);Creatinine (g1:\>ULN-1.5\*ULN, g2:\>1.5-3\*ULN, g3:\>3 6\*ULN, g4:\>6\*ULN);hyperglycemia (g1:\>ULN-160,g2:\>160 250, g3:\>250 500,g4:\>500mg/dL); bilirubin(total) (g1:\>ULN-1.5\*ULN, g2:\>1.5-3\*ULN, g3:\>3 10\*ULN,g4:\>10\*ULN); hypoglycaemia (g1:\<LLN-55, g2:\<55-40, g3:\<40 30, g4:\<30mg/dL); hyperkalemia (g1:\>ULN-5.5,g2:\>5.5-6, g3:\>6 7,g4:\>7mmol/L); hypokalemia (g1:\<LLN-3,g2:\<LLN-3,g3:\<3 2.5, g4:\<2.5mmol/L); hypermagnesemia (g1:\>ULN-3,g3:\>3 8,g4:\>8mg/dL); hypocalcemia (g1:\<LLN-8,g2:\<8-7, g3:\<7-6, g4:\<6mg/dL); hypercalcemia (g1:\>ULN-11.5,g2:\>11.5-12.5, g3:\>12.5-13.5, g4:\>13.5mg/dL);hypomagnesemia (g1:\<LLN-1.2,g2:\<1.2-0.9, g3:\<0.9-0.7,g4:\<0.7mg/dL); hyponatremia (g1:\<LLN-130,g3:\<130-120, g4:\<120mmol/L);hypoalbuminemia (g1:\<LLN-3,g2:\<3-2, g3:\<2, g4:lifethreatening);hypophosphatemia (g1:\<LLN-2.5,g2:\<2.5-2,g3:\<2-1,g4:\<1mg/dL).
Percentage of Participants Achieving SVR ≥50% as Measured by MRI/CT Scan at Week 24 in the Randomized Cohort Week 24 The double blind, randomized, placebo controlled phase of the study was not enrolled after the study was terminated early so no data were collected to assess this endpoint.
Kaplan-Meier Estimate of Overall Survival in the Randomized Cohort Baseline to end of treatment The double blind, randomized, placebo controlled phase of the study was not enrolled after the study was terminated early so no data were collected to assess this endpoint.
Glasdegib PK Parameters in the Randomized Cohort Cycle 1, Day 15 The double blind, randomized, placebo controlled phase of the study was not enrolled after the study was terminated early so no data were collected to assess this endpoint.
Number of Participants With Treatment -Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Randomized Cohort Baseline up to Week 131 An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. 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/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state.
Number of Participants With Treatment Emergent Adverse Events (AEs) According to Maximum Severity: Randomized Cohort Baseline up to Week 131 AE was untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. SAE was AE resulting in any of 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/incapacity; congenital anomaly. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AE were assessed according to maximum severity grading based on NCI CTCAE Version 4.03.Grade 1=mild; Grade 2=moderate; within normal limits. Grade 3=severe or medically significant but not immediately life-threatening; Grade 4=life-threatening or disabling; urgent intervention indicated; Grade 5=death.
Psychometric Validation of the MPN-SAD in the Randomised Cohort Baseline to end of treatment The double blind, randomized, placebo controlled phase of the study was not enrolled after the study was terminated early so no data were collected to assess this endpoint.
Trial Locations
- Locations (19)
Herbert Irving Comprehensive Cancer Center-Columbia University Medical Center
🇺🇸New York, New York, United States
Weill Cornell Medical College - New York-Presbyterian Hospital
🇺🇸New York, New York, United States
Weill Cornell Medical College-New York Presbyterian Hospital
🇺🇸New York, New York, United States
UCSD Medical Center Clinical Laboratory - La Jolla
🇺🇸La Jolla, California, United States
University of California San Diego (UCSD) Moores Cancer Center
🇺🇸La Jolla, California, United States
Cleveland Clinic - Taussig Cancer Institute
🇺🇸Cleveland, Ohio, United States
Mayo Clinic Hospital
🇺🇸Phoenix, Arizona, United States
UC San Diego Medical Center- Hillcrest
🇺🇸San Diego, California, United States
Huntsman Cancer Institute-University of Utah
🇺🇸Salt Lake City, Utah, United States
University of Utah, Huntsman Cancer Hospital
🇺🇸Salt Lake City, Utah, United States
Kobe University Hospital
🇯🇵Kobe, Hyogo, Japan
Tokyo Medical University Hospital
🇯🇵Tokyo, Japan
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Froedtert Hospital and Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Osaka University Hopsital
🇯🇵Suita-Shi, Osaka, Japan
Mayo Clinic Building - Phoenix
🇺🇸Phoenix, Arizona, United States
Juntendo University Hospital
🇯🇵Bunkyo-ku, Tokyo, Japan
Mayo Clinic
🇺🇸Scottsdale, Arizona, United States
UC San Diego Moores Cancer Center - Investigational Drug Services
🇺🇸La Jolla, California, United States