Clinical trial NCT04839393: 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
Official title: A PHASE 1, OPEN-LABEL STUDY TO EVALUATE THE PHARMACOKINETIC INTERACTIONS BETWEEN PF-06882961 AND PF-06865571 IN HEALTHY ADULT PARTICIPANTS (PART A) AND OVERWEIGHT ADULTS OR ADULTS WITH OBESITY WHO ARE OTHERWISE HEALTHY (PART B)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteer
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2021-04-09
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

1. 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.
2. 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.
3. Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
4. 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.
5. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICD and in this protocol.

Exclusion Criteria

1. 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).
2. Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy, bariatric surgery, active inflammatory bowel disease, or an intestinal resection).
3. 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.
4. Known intolerance or hypersensitivity to GLP-1 receptor agonists.
5. Known intolerance or hypersensitivity to DGAT2 inhibitors.
6. 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.
7. 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.
8. 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).
9. 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.
10. Acute pancreatitis or history of chronic pancreatitis.
11. Symptomatic gallbladder disease.
12. Medical history or characteristics suggestive of genetic or syndromic obesity or obesity induced by other endocrinological disorders (eg, Cushing Syndrome).
13. History of major depressive disorder or history of other severe psychiatric disorders (eg, schizophrenia or bipolar disorder) within the last 2 years from screening.
14. 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.
15. History of HIV infection.
16. Any lifetime history of a suicide attempt.
17. Use of prescription or nonprescription drugs and dietary and herbal supplements within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention.
18. Prohibited prior/concomitant medication as per protocol.
19. Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of study intervention used in this study (whichever is longer). An emergency use authorized or approved COVID-19 vaccine is considered a concomitant medication.
20. Known prior participation in a clinical trial with PF-06882961 or PF-06865571.
21. Part B only: A Patient Health Questionnaire (PHQ-9) score ≥15 obtained at Screening or Day -1.
22. Part B only: Response of "yes" to question 4 or 5, or on any behavioral question on the C-SSRS at Screening or Day -1.
23. A positive urine drug test.
24. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest. If BP is ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.
25. Screening 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, baseline QTc interval \>450 msec, complete LBBB, signs of an acute or indeterminate-age myocardial infarction, ST-T interval changes suggestive of myocardial ischemia, second- or third-degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If the baseline uncorrected QT interval is \>450 msec, this interval should be rate-corrected using the Fridericia method and the resulting QTcF should be used for decision making and reporting. If QTc exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be repeated 2 more times and the average of the 3 QTc or QRS values should be used to determine the participant's eligibility. Computer-interpreted ECGs should be overread by a physician experienced in reading ECGs before excluding participants.
26. A positive COVID-19 test at or after screening.
27. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study-specific laboratory and confirmed by a single repeat test, if deemed necessary: HbA1c ≥6.5%. AST or ALT \> ULN. Total bilirubin level \> ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and are eligible for this study provided the direct bilirubin level is ≤ ULN.

    TSH \> ULN or \< LLN. Serum calcitonin \> ULN. Amylase or lipase \> ULN. Fasting blood glucose ≥126 mg/dL. Fasting triglycerides \>200 mg/dL. INR \> ULN. PLT \< LLN. eGFR \<80 mL/min/1.73 m2 as calculated by the CKD-EPI equation. Positive testing for HIV, HepBsAg, or HCVAb. Study participants positive for HCVAb are to be excluded unless known to have been treated with a known curative therapy and negative for HCV RNA. Hepatitis B vaccination is allowed.
28. Participation in a formal weight reduction program (eg, Weight Watchers) within 90 days prior to Screening.
29. History of alcohol abuse or binge drinking and/or any other illicit drug use or dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5 (male) and 4 (female) or more alcoholic drinks in about 2 hours. As a general rule, alcohol intake should not exceed 14 units per week (1 unit = 8 ounces (240 mL) beer, 1 ounce (30 mL) of 40% spirit or 3 ounces (90 mL) of wine).
30. Current use of tobacco or nicotine containing products in excess of the equivalent of 5 cigarettes per day.
31. Known or suspected illicit drug use.
32. Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dose randomization (Day -1).
33. History of sensitivity to heparin or heparin-induced thrombocytopenia if Hep-lock is used for IV blood draw.
34. Unwilling or unable to comply with the criteria in the Lifestyle Considerations section of this protocol.
35. Investigator site staff or Pfizer employees directly involved in the conduct of the study, site staff otherwise supervised by the investigator, and their respective family members.

Primary outcomes:
measure: Part A: PF-06882961 Maximum Observed Concentration (Cmax)
timeFrame: 0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 and 24 hours post-dose on Day 1
measure: Part A: PF-06882961 Area Under the Plasma Concentration-time Profile From Time 0 to the Time 24 Hours Post-dose (AUC24)
timeFrame: 0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16 and 24 hours post-dose on Day 1
measure: Part B: PF-06865571 Cmax on Day 1 and Day 47
timeFrame: 0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24 and 48 hours post-dose
measure: 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
timeFrame: 0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24 and 48 hours post-dose
measure: 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
timeFrame: 0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 24 and 48 hours post-dose
measure: Part B: PF-06882961 Cmax on Day 46 and Day 61
timeFrame: 0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose
measure: 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
timeFrame: 0 (prior to dosing), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours post-dose
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) in Part A
timeFrame: Up to 68 days
measure: Number of Participants With Clinical Laboratory Abnormalities in Part A
timeFrame: From Screening (28 days prior to the day of treatment) to Day 2 of Period 2, for a maximum of 33 Days
measure: Number of Participants With Vital Signs Data Meeting Pre-specified Criteria in Part A
timeFrame: From Screening (28 days prior to the day of treatment) to Day 2 of Period 2, for a maximum of 33 Days
measure: Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria in Part A
timeFrame: From Screening (28 days prior to the day of treatment) to Day 2 of Period 2, for a maximum of 33 Days
measure: Number of Participants With TEAEs in Part B
timeFrame: Up to 173 days
measure: Number of Participants With Clinical Laboratory Abnormalities in Part B
timeFrame: From Screening (28 days prior to follow-up visit (up to 10 days after the last dose of treatment), for a maximum of 148 Days
measure: Number of Participants With Vital Signs Data Meeting Pre-specified Criteria in Part B
timeFrame: From Screening (28 days prior to follow-up visit (up to 10 days after the last dose of treatment), for a maximum of 148 Days
measure: Change From Baseline in Body Weight for Participants in Part B
timeFrame: At Baseline (Days -28 to 2), on Period 2, Days 6, 13, 20 ,27, 34, and 41, Period 4, Days 9 and14 and follow-up visit (Days 68-71)
measure: Number of Participants With ECG Data Meeting Pre-specified Criteria in Part B
timeFrame: From Screening (28 days prior to follow-up visit (up to 10 days after the last dose of treatment), for a maximum of 148 Days
measure: Number of Participants With Suicidal Ideation or Behavior as Per C-SSRS Mapped to Columbia Classification Algorithm of Suicide Assessment (C-CASA) in Part B
timeFrame: At Screening (Days -28 to -2), Baseline (Period 1 Day -1), on Period 2, Days 6, 13, 20, 27, 34 and 41, Period 4, Days 2, 9 and 14 and follow-up visit (Days 68-71)
measure: Number of Participants With Response to PHQ-9 in Part B
timeFrame: At Screening (Days -28 to -2), Baseline (Period 1 Day -1), on Period 2, Days 6, 13, 20, 27, 34 and 41, Period 4, Days 2, 9 and 14 and follow-up visit (Days 68-71)
Other outcomes:
Locations:
city: Tustin
country: United States
facility: Orange County Research Center
state: California
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: