Multiple Escalating Oral Doses Study of PF-07081532 in Adult Participants With Type 2 Diabetes Mellitus

Phase 1

Completed

Conditions: Diabetes Mellitus Type 2

Interventions: Other: Placebo
Drug: PF-07081532
Drug: Clopidogrel

Registration Number: NCT04305587

Lead Sponsor: Pfizer

Brief Summary: This is a randomized, placebo-controlled, double-blind (investigator- and participant-blinded), sponsor-open, dose-escalating study of PF-07081532 in patients with Type 2 diabetes on metformin (Parts A and C). The study may also enroll non-diabetic participants with obesity (Part B). Study participants will receive an investigational product or placebo every day for up to 28 days (Part A) or up to 42 days (Part B, optional; Part C, optional).

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of multiple oral doses of PF-07081532 in participants with inadequately controlled T2DM on metformin and optionally in non-diabetic obese participants.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 66

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active Obesity	Placebo	Part B
Placebo Obesity	Placebo	Part B
Active T2DM	PF-07081532	Parts A and C
Placebo T2DM	PF-07081532	Parts A and C
Placebo Obesity	Clopidogrel	Part B
Active Obesity	Clopidogrel	Part B

Primary Outcome Measures

Name	Time	Method
Number of Participants With Vital Signs Abnormalities	From Baseline to 7-14 days following last dose administration (that is a maximum of 42 days from baseline for Part A and a maximum of 56 days from baseline for Part B and Part C)	Vital signs (pulse rate, systolic and diastolic blood pressure) were obtained with participant in the supine position. The pre-specified categorical analysis criteria in vital signs, were supine systolic blood pressure \< 90 millimeters of mercury (mmHg), supine systolic blood pressure increase/decrease from baseline ≥ 30mmHg; supine diastolic blood pressure \<50 mmHg, supine diastolic blood pressure increase/decrease from baseline ≥ 20mmHg; pulse rate \<40 beats per minute (bpm) or \>120 bpm.
Number of Participants With Treatment Emergent Treatment-Related Adverse Events	From the first dose up to 28-35 days after last administration of study intervention (that is a maximum of 63 days from first dose for Part A and a maximum of 77 days from first dose for Part B and Part C)	An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. Treatment-related AE was any untoward medical occurrence attributed to study intervention in a participant who received study intervention. Treatment-emergent are events between first dose of study intervention and up to 28-35 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Number of Participants With Laboratory Abnormalities	From Baseline to 7-14 days following last dose administration (that is a maximum of 42 days from baseline for Part A and a maximum of 56 days from baseline for Part B and Part C)	Participants with laboratory abnormalities with ≥2 occurrences (without regard to baseline abnormality) that met pre-specified criteria were High-density lipoprotein (HDL) Cholesterol \<0.8✕ lower limit of normal (LLN); Bicarbonate \<0.9✕LLN; Calcitonin\>1.0✕upper limit of normal (ULN); Triglycerides \>1.3✕ULN; Aspartate Aminotransferase \>3.0✕ULN; Low-density lipoprotein (LDL) Cholesterol \>1.2✕ULN; Urine Glucose ≥1; Urine Ketones ≥1; Urine Leukocyte Esterase ≥1; Urine Leukocytes ≥20; Urine Hyaline Casts \>1; Urine Hemoglobin ≥1; and Urine Nitrite ≥1.
Number of Participants With Abnormal Electrocardiogram (ECG)	From Baseline to 7-14 days following last dose administration (that is a maximum of 42 days from baseline for Part A and a maximum of 56 days from baseline for Part B and Part C)	The pre-specified categorical analysis criteria in ECG, were PR interval: value ≥ 300 milliseconds (msec), percentage change ≥ 25/50%; QRS duration: value ≥140 msec, percentage change ≥ 50%; QTcF interval: 450 \< value ≤ 480 msec, 480 \< value ≤ 500 msec, value \>500 msec, and 30\<change ≤ 60 msec, change \>60 msec.

Secondary Outcome Measures

Name	Time	Method
Area Under the Curve From Time 0 to 24 Hours (AUC24) Post Dose for PF-07081532	0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Days 1 and 28 for Part A, on Days 1 and 42 for Part B and Part C	AUC24 is defined as area under the concentration-time profile from time 0 to 24 hours using Linear/Log trapezoidal method.
Cumulative Amount of Drug Recovered Unchanged in Urine Over 24 Hours (Ae24) for PF-07081532	Part A: Day 28 (0-24 hours). Part C : Day 42 (0-24 hours)	Ae24 is defined as cumulative amount of drug recovered unchanged in urine over 24 hours using the method of urine concentration \* volume of urine.
Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-07081532	0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Days 1 and 28 for Part A, on Days 1 and 42 for Part B and Part C	Tmax is defined as time for Cmax observed directly from data as time of first occurrence.
Time Measured for the Plasma Concentration to Decrease by One-Half (t1/2) for PF-07081532	0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Day 28 for Part A, on Day 42 for Part B and Part C	t1/2 is defined as the time measured for the plasma concentration to decrease by one half.
Maximum Observed Plasma Concentration (Cmax) for PF-07081532	0, 0.5, 1, 2, 4, 6, 8, 10, 12, 16, 24 hours post-dose on Days 1 and 28 for Part A, on Days 1 and 42 for Part B and Part C	Cmax is defined as maximum plasma concentration observed directly from data.
Percentage of Ae24 (Ae24%) for PF-07081532	Part A: Day 28 (0-24 hours). Part C : Day 42 (0-24 hours)	Ae24% is defined as percent of dose recovered unchanged in urine over the 24 hours using the method of 100 \* Ae24/Dose
Renal Clearance (CLr) for PF-07081532	Part A: Day 28 (0-24 hours). Part C : Day 42 (0-24 hours)	Renal clearance was calculated as cumulative amount of drug recovered unchanged in urine over the dosing interval tau (Aetau) divided by area under the concentration time-curve from time 0 to time tau (AUCtau)