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

Diabetes Mellitus Type 2 Clinical Trial

Official title:

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-07081532 in Adult Participants With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04305587
• Other study ID #: C3991002
• Status: Completed
• Phase: Phase 1
• Start date: March 16, 2020
• Est. completion date: July 14, 2021

Study information

• Verified date: June 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: July 14, 2021
• Est. primary completion date: July 14, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Key Inclusion Criteria for participants enrolling with T2DM:

• Type 2 Diabetes treated with a stable dose of metformin at least 500 mg per day for at least 2 months prior to screening visit and use of no other medications for glycemic control.

• HbA1c value between 7.0% and 10.5%, inclusive.

Key Exclusion Criterion for participants enrolling with T2DM:

-Type 1 Diabetes or secondary forms of diabetes.

Key Inclusion Criterion for participants enrolling with obesity:

-Obese (as indicated by screening BMI) non-diabetic adults.

Key Exclusion Criterion for participants enrolling with obesity:

--Type 1 or Type 2 Diabetes or secondary forms of diabetes.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus Type 2
• Diabetes Mellitus, Type 2

Intervention

Drug:
• PF-07081532
Investigational Drug once daily for up to 42 days; multiple ascending dose design.

Other:
• Placebo
Placebo once daily for up to 42 days.

Drug:
• Clopidogrel
Part B may include a drug-drug interaction study using open-label clopidogrel. Clopidrogrel may be given as two single doses of 75 mg administered on day -2 and day 41.

Locations

Country	Name	City	State
United States	Anaheim Clinical Trials, LLC	Anaheim	California
United States	Qps-Mra, Llc	South Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment Emergent Treatment-Related Adverse Events	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.	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)
Primary	Number of Participants With Laboratory Abnormalities	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.	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)
Primary	Number of Participants With Vital Signs Abnormalities	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.	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)
Primary	Number of Participants With Abnormal Electrocardiogram (ECG)	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	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)
Secondary	Area Under the Curve From Time 0 to 24 Hours (AUC24) Post Dose for PF-07081532	AUC24 is defined as area under the concentration-time profile from time 0 to 24 hours using Linear/Log trapezoidal method.	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
Secondary	Maximum Observed Plasma Concentration (Cmax) for PF-07081532	Cmax is defined as maximum plasma concentration observed directly from data.	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
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) for PF-07081532	Tmax is defined as time for Cmax observed directly from data as time of first occurrence.	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
Secondary	Time Measured for the Plasma Concentration to Decrease by One-Half (t1/2) for PF-07081532	t1/2 is defined as the time measured for the plasma concentration to decrease by one half.	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
Secondary	Cumulative Amount of Drug Recovered Unchanged in Urine Over 24 Hours (Ae24) for PF-07081532	Ae24 is defined as cumulative amount of drug recovered unchanged in urine over 24 hours using the method of urine concentration * volume of urine.	Part A: Day 28 (0-24 hours). Part C : Day 42 (0-24 hours)
Secondary	Percentage of Ae24 (Ae24%) for PF-07081532	Ae24% is defined as percent of dose recovered unchanged in urine over the 24 hours using the method of 100 * Ae24/Dose	Part A: Day 28 (0-24 hours). Part C : Day 42 (0-24 hours)
Secondary	Renal Clearance (CLr) for PF-07081532	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)	Part A: Day 28 (0-24 hours). Part C : Day 42 (0-24 hours)

External Links

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