A Phase 1, Randomized, Double-Blind, Sponsor-Open, Placebo-Controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of Multiple Escalating Oral Doses of PF-06954522 in Adult Participants With Type 2 Diabetes Mellitus
Overview
- Phase
- Phase 1
- Intervention
- Placebo
- Conditions
- Type 2 Diabetes Mellitus (T2DM)
- Sponsor
- Pfizer
- Enrollment
- 50
- Locations
- 2
- Primary Endpoint
- Number of Participants Reporting Adverse Events
- Status
- Completed
- Last Updated
- 11 months ago
Overview
Brief Summary
The purpose of the study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of multiple escalating oral doses of PF-06954522 in adult participants with inadequately controlled type 2 diabetes mellitus (T2DM) on metformin (Part A) and optionally in non-diabetic participants with obesity (Part B).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female participants of non-childbearing potential and males between the ages of 18 and 70 years, inclusive, at the time of signing the ICD.
- •Part A only: Diagnosis of Diabetes - Participants enrolling with T2DM must have a clinical history of T2DM and be taking metformin monotherapy as their only anti-hyperglycemic treatment. Metformin dose must be at least 500 mg per day and must be stable, defined as no change in the treatment, including dose, for at least 2 months prior to the screening visit.
- •Part C only: Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
- •Part A only: For participants enrolling with T2DM: HbA1c ≥7.0% and ≤10.5% at screening (confirmed by a single repeat, if necessary).
- •Part B and C only: For participants enrolling as non-diabetic with obesity (Part B), or healthy (Part C): HbA1c \<6.5% at screening.
- •All participants must have a total body weight \>50 kg (110 lbs).
- •Parts A and B only: Stable body weight, defined as \<5 kg change (per participant report) for 90 days prior to screening
- •Part A only: For participants enrolling with T2DM: BMI ≥24.5 to ≤45.5 kg/m
- •Part B only: For participants enrolling as non-diabetic with obesity: BMI \>30.5 to ≤45.5 kg/m2
- •Part C only: For participants enrolling as healthy: BMI 20-30.5 kg/m2
Exclusion Criteria
- •Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, hepatic, psychiatric, neurological, dermatological, or allergic disease (including drug allergies but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
- •Parts A and B only: Participants with T2DM (Part A) or obesity (Part B) are allowed. Participants who have chronic conditions other than T2DM and obesity (eg, hypercholesterolemia or hypertension) but are controlled by either diet or stable doses of 2 or fewer medications may be included (eg, a participant with hypercholesterolemia on appropriate treatment is eligible).
- •Any condition possibly affecting drug absorption (eg, prior bariatric surgery, gastrectomy, or any area of intestinal resection, active inflammatory bowel disease or pancreatic insufficiency).
- •History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed.
- •Diagnosis of type 1 diabetes mellitus or secondary forms of diabetes.
- •Parts B and C only: Participants enrolling as non-diabetic with obesity (Part B) or healthy (Part C) may not have medical history of T2DM.
- •Evidence or history of clinically significant cardiovascular disease. In particular, history of myocardial infarction, unstable angina, arterial revascularization, stroke, New York Heart Association Functional Class II IV heart failure, or transient ischemic attack within 6 months of screening.
- •Any malignancy not considered cured (except basal cell carcinoma and squamous cell carcinoma of the skin); a participant is considered cured if there has been no evidence of cancer recurrence in the previous 5 years.
- •Acute pancreatitis or history of chronic pancreatitis.
- •Acute gallbladder disease.
Arms & Interventions
Part A
Multiple doses of PF 06954522 or placebo daily for up to 8 weeks in adult participants with T2DM in up to 7 cohorts.
Intervention: Placebo
Part A
Multiple doses of PF 06954522 or placebo daily for up to 8 weeks in adult participants with T2DM in up to 7 cohorts.
Intervention: PF-06954522
Part B (Optional)
Multiple doses of PF 06954522 or placebo daily for up to 8 weeks in non-diabetic adult participants with obesity in up to 3 cohorts.
Intervention: Placebo
Part B (Optional)
Multiple doses of PF 06954522 or placebo daily for up to 8 weeks in non-diabetic adult participants with obesity in up to 3 cohorts.
Intervention: PF-06954522
Part C (Optional)
An 8-period multiple-dose assessment of the effect of PF-06954522 on rosuvastatin, midazolam, and omeprazole PK in healthy adult participants for up to 14 weeks in healthy adult participants.
Intervention: Rosuvastatin
Part C (Optional)
An 8-period multiple-dose assessment of the effect of PF-06954522 on rosuvastatin, midazolam, and omeprazole PK in healthy adult participants for up to 14 weeks in healthy adult participants.
Intervention: Midazolam
Part C (Optional)
An 8-period multiple-dose assessment of the effect of PF-06954522 on rosuvastatin, midazolam, and omeprazole PK in healthy adult participants for up to 14 weeks in healthy adult participants.
Intervention: Omeprazole
Part C (Optional)
An 8-period multiple-dose assessment of the effect of PF-06954522 on rosuvastatin, midazolam, and omeprazole PK in healthy adult participants for up to 14 weeks in healthy adult participants.
Intervention: PF-06954522
Outcomes
Primary Outcomes
Number of Participants Reporting Adverse Events
Time Frame: Baseline through Week 14
Number of Participants with Clinically Significant Change From Baseline in Laboratory Abnormalities
Time Frame: Baseline through Week 14
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
Time Frame: Baseline through Week 14
Number of Participants With Clinically Significant Change From Baseline in 12-Lead ECGs
Time Frame: Baseline through Week 14
Number of Participants with categorical scores on the Columbia Suicide Severity Rating Scale (C-SSRS)
Time Frame: Baseline through Week 14
Secondary Outcomes
- Maximum Observed Plasma Concentration (Cmax)(Part A: Days -1, 1, 14, 21 & 28. Days 2, 4, 7, 10, 17, 20, 24, 30. Part A & B: Days -1, 1, 28, 49 & 56. Days 7, 14, 21, 35, 42, 57 & 58. Part C: Period 3 Day 3 & Period 5 Day 28)
- Area Under the Curve from Time Zero to end of dosing interval (AUCtau)(Part A: Days -1, 1, 14, 21 & 28. Days 2, 4, 7, 10, 17, 20, 24, 30. Part A & B: Days -1, 1, 28, 49 & 56. Days 7, 14, 21, 35, 42, 57, 58. Part C: Period 3 Day 3 & Period 5 Day 28)
- Time to Reach Maximum Observed Plasma Concentration (Tmax)(Part A: Days -1, 1, 14, 21 & 28. Days 2, 4, 7, 10, 17, 20, 24 & 30. Part A & B: Day -1, 1 28, 49 & 56. Days 7, 14, 21, 35, 42, 57 & 58. Part C: Period 3 Day 3 & Period 5 Day 28)
- Plasma Decay Half-Life (t1/2)(Part A: Day -1, 1,14, 21 & 28. Days 2, 4, 7, 10, 17, 20, 24 & 30. Part A & B: Day -1, 1, 28, 49 & 56. Days 7, 14, 21, 35, 42, 57 & 58. Part C: Period 3 Day 3 & Period 5 Day 28)
- Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau)(Part A: Day 28. Part A & B: Day 56)
- Percentage of Dose of PF-06751979 Excreted Unchanged in the Urine Over the Dosing Interval Tau (Aetau%)(Part A: Day 28. Part A & B: Day 56)
- Renal Clearance (CLr)(Part A: Day 28. Part A & B: Day 56)