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

Last updated date
Study Location
Orange County Research Center
Tustin, California, 92780, United States
Contact
1-800-718-1021
ClinicalTrials[email protected]

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Healthy Volunteer
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18-65 years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


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.

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Advanced Information
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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)
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Masking Description:
None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Healthy Volunteer
Intervention  ICMJE
  • Drug: PF-06882961 followed by PF-06882961/PF-06865571
    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.
  • Drug: PF-06882961/PF-06865571 followed by PF-06882961
    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.
  • Drug: PF-06882961 + PF-06865571
    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)
Study Arms  ICMJE
  • Experimental: Part A - Sequence 1
    Treatment A - PF-06882961 single dose followed by Treatment B - PF-06882961 single dose and PF-06865571 single dose
    Intervention: Drug: PF-06882961 followed by PF-06882961/PF-06865571
  • Experimental: Part A - Sequence 2
    Treatment B - PF-06882961 single dose and PF-06865571 single dose followed by Treatment A - PF-06882961 single dose
    Intervention: Drug: PF-06882961/PF-06865571 followed by PF-06882961
  • Experimental: Part B
    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
    Intervention: Drug: PF-06882961 + PF-06865571
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 7, 2021)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2, 2021
Estimated Primary Completion Date September 2, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Pfizer CT.gov Call Center1-800-718-1021[email protected]
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04839393
Other Study ID Numbers  ICMJE C3421038
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD:No
Plan Description:Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/d….
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director:Pfizer CT.gov Call CenterPfizer
PRS Account Pfizer
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP