A Drug-Drug Interaction Study Between PF-06882961 and PF-06865571 in Healthy Adult Participants and Overweight Adults or Adults With Obesity Who Are Otherwise Healthy

NCT04839393 | Completed Phase 1 Results FDA Drug

• 1 other identifier: C3421038
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be conducted in 2 parts. Part A will investigate the potential effect of PF-06865571 on the pharmacokinetics (PK) of PF-06882961 in healthy adult participants. Part B will evaluate the effect of PF-06882961 on the PK of PF-06865571, as well as the effect of PF-06865571 on the PK of PF-06882961 in overweight adults or adults with obesity who are otherwise healthy.

Conditions

Healthy Volunteer

Outcome Measures

Primary Outcomes (7)

• Part A: PF-06882961 Maximum Observed Concentration (Cmax)

  Cmax for PF-06882961 was observed directly from data.

  0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 and 24 hours post-dose on Day 1

• Part A: PF-06882961 Area Under the Plasma Concentration-time Profile From Time 0 to the Time 24 Hours Post-dose (AUC24)

  AUC24 for PF-06882961 was determined by Linear/Log trapezoidal method.

  0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 and 24 hours post-dose on Day 1

• Part B: PF-06865571 Cmax on Day 1 and Day 47

  Cmax for PF-06865571 was observed directly from data on Day 1 and Day 47.

  0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24 and 48 hours post-dose

• Part B: PF-06865571 Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) on Day 1 and Day 47

  AUClast for PF-06865571 was determined by Linear/Log trapezoidal method on Day 1 and Day 47.

  0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24 and 48 hours post-dose

• Part B: PF-06865571 Area Under the Plasma Concentration-time Profile From Time 0 Extrapolated to Infinite Time (AUCinf) on Day 1 and Day 47

  AUCinf for PF-06865571 was calculated as AUClast + (Clast\*/kel) on Day 1 and Day 47. Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis and kel was the elimination rate constant.

  0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24 and 48 hours post-dose

• Part B: PF-06882961 Cmax on Day 46 and Day 61

  Cmax for PF-06882961 was observed directly from data on Day 46 and Day 61.

  0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose

• Part B: PF-06882961 Area Under the Plasma Concentration-time Profile From Time 0 to the Time 12 Hours Post-dose (AUC12) on Day 46 and Day 61

  AUC 12 for PF-06882961 was determined by Linear/Log trapezoidal method on Day 46 and Day 61.

  0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose

Secondary Outcomes (11)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in Part A

  Up to 68 days

• Number of Participants With Clinical Laboratory Abnormalities in Part A

  From Screening (28 days prior to the day of treatment) to Day 2 of Period 2, for a maximum of 33 Days

• Number of Participants With Vital Signs Data Meeting Pre-specified Criteria in Part A

  From Screening (28 days prior to the day of treatment) to Day 2 of Period 2, for a maximum of 33 Days

• Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria in Part A

  From Screening (28 days prior to the day of treatment) to Day 2 of Period 2, for a maximum of 33 Days

• Number of Participants With TEAEs in Part B

  Up to 173 days

Study Arms (3)

Part A - Sequence 1

EXPERIMENTAL

Treatment A - PF-06882961 single dose followed by Treatment B - PF-06882961 single dose and PF-06865571 single dose

Drug: PF-06882961 followed by PF-06882961/PF-06865571

Part A - Sequence 2

EXPERIMENTAL

Treatment B - PF-06882961 single dose and PF-06865571 single dose followed by Treatment A - PF-06882961 single dose

Drug: PF-06882961/PF-06865571 followed by PF-06882961

Part B

EXPERIMENTAL

Period 1: PF-06865571 single dose, Period 2: PF-06882961 twice daily dose titration, Period 3: PF-06865571 single dose and PF-06882961 twice daily dosing, Period 4: PF-06865571 twice daily dosing and PF-06882961 twice daily dosing

Drug: PF-06882961 + PF-06865571

Interventions

PF-06882961 followed by PF-06882961/PF-06865571 DRUG

Treatment A - PF-06882961 20 mg single dose followed by Treatment B - PF-06882961 20 mg single dose plus PF-06865571 300 mg single dose. There will be a washout interval between periods of at least 3 days.

Part A - Sequence 1

PF-06882961/PF-06865571 followed by PF-06882961 DRUG

Treatment B - PF-06882961 20 mg single dose plus PF-06865571 300 mg single dose followed by Treatment A - PF-06882961 20 mg single dose. There will be a washout interval between periods of at least 3 days.

Part A - Sequence 2

PF-06882961 + PF-06865571 DRUG

Period 1: PF-06865571 300 mg single dose (Day 1), Period 2: PF-06882961 10 mg twice daily dose titration up to 200 mg twice daily dosing (Days 3-46), Period 3: PF-06865571 300 mg single dose (Day 47) and PF-06882961 200 mg twice daily dosing (Days 47-48), Period 4: PF-06865571 300 mg twice daily dosing and PF-06882961 200 mg twice daily dosing (Days 49-62)

Part B

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female participants must be 18 to 65 years of age, inclusive, at the time of signing the ICD.
• Women can be of child-bearing potential, however, cannot be pregnant, breastfeeding, or planning to become pregnant while participating in the study.
• Male and female participants who are overtly healthy (other than being overweight or obese in Part B only) as determined by medical evaluation including medical history, physical examination, and laboratory tests.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• BMI and total body weight:
• Part A: BMI of 17.5 to 30.5 kg/m2; and a total body weight \>50 kg (110 lb); Part B: BMI ≥25 kg/m2 and not more than 40 kg/m2 at Screening; stable body weight, defined as \<5 kg change (per participant report) for 90 days before Screening.
• Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

You may not qualify if:

• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).
• Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy, bariatric surgery, active inflammatory bowel disease, or an intestinal resection).
• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions or situations related to COVID-19 pandemic (eg, contact with positive case, residence or travel to an area with high incidence) that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
• Known intolerance or hypersensitivity to GLP-1 receptor agonists.
• Known intolerance or hypersensitivity to DGAT2 inhibitors.
• Diagnosis of type 1 or type 2 diabetes mellitus or secondary forms of diabetes at screening. Note: women with prior diagnoses of gestational diabetes during pregnancy only are eligible if they meet the other eligibility criteria.
• 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 study participant is considered cured if there has been no evidence of cancer recurrence in the previous 5 years (from Screening).
• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2, or study participants with suspected medullary thyroid carcinoma per the investigator's judgment.
• Acute pancreatitis or history of chronic pancreatitis.
• Symptomatic gallbladder disease.
• Medical history or characteristics suggestive of genetic or syndromic obesity or obesity induced by other endocrinological disorders (eg, Cushing Syndrome).
• History of major depressive disorder or history of other severe psychiatric disorders (eg, schizophrenia or bipolar disorder) within the last 2 years from screening.
• Known medical history of active liver disease (other than non-alcoholic hepatic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, alcoholic liver disease, primary sclerosing cholangitis, autoimmune hepatitis, overlap syndrome, or prior known drug-induced liver injury.
• History of HIV infection.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Orange County Research Center

Tustin, California, 92780, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

danuglipron; ervogastat

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: None (Open Label)
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2021
• First Posted: April 9, 2021
• Study Start: April 5, 2021
• Primary Completion: October 10, 2021
• Study Completion: November 8, 2021
• Last Updated: August 21, 2023
• Results First Posted: August 21, 2023

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)