STUDY TO EVALUATE THE EFFECT OF PF-06882961 ON SINGLE DOSE ATORVASTATIN, MEDAZOLAM AND ORALCONTRACEPTIVE PHARMACOKINETICS IN HEALTHY ADULT PARTICIPANTS

NCT05093205 | Completed Phase 1 Results FDA Drug

• 1 other identifier: C3421047
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to characterize the effect of PF-06882961, administered at 2 steady-state dose levels, on the PK of single doses of atorvastatin (20 mg) or midazolam (5 mg), administered separately, in healthy adult male and female participants (Part A), or an OC in healthy PM female participants (Part B).

Conditions

Healthy Adults

Outcome Measures

Primary Outcomes (4)

• (Part A) Area Under the Concentration-time Curve From Time 0 to Infinity (AUCinf) of Atorvastatin in Periods 1, 4, and 7

  Atorvastatin was given on Day 1 in Periods 1, 4 and 7 of Part A and blood samples were collected for atorvastatin pharmacokinetic (PK) at the preset time points described in the Time Frame. AUCinf calculated area under the plasma concentration-time profile from time 0 extrapolated to infinite time.

  For Part A Periods 1, 4, and 7: At 0 (prior to atorvastatin dose), 0.5, 1, 1.5, 2, 4, 6, 9, 12, 24, 36, 48, 72 hours (only Periods 1 & 4) post atorvastatin dose on Day 1 of each period.

• (Part A) AUCinf of Midazolam in Periods 2, 5, and 8

  Midazolam was given on Day 1 in Periods 2, 5 and 8 of Part A and blood samples were collected for midazolam PK at the preset time points described in the Time Frame. AUCinf calculated area under the plasma concentration-time profile from time 0 extrapolated to infinite time.

  For Part A Periods 2, 5, and 8: At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours (only for Periods 2 & 5) post midazolam dose on Day 1 of each period.

• (Part B) AUCinf of Levonorgestrel in Periods 1, 3 and 5

  Levonorgestrel was given on Day 1 in Periods 1, 3 and 5 of Part B and blood samples were collected for levonorgestrel PK at the preset time points described in the Time Frame. AUCinf calculated area under the plasma concentration-time profile from time 0 extrapolated to infinite time.

  For Part B Periods 1, 3, 5: At 0 (prior to levonorgestrel dose), 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96, 120 hours post levonorgestrel dose on Day 1 of each period.

• (Part B) AUCinf of Ethinyl Estradiol in Periods 1, 3 and 5

  Ethinyl estradiol (EE) was given on Day 1 in Periods 1, 3 and 5 of Part B and blood samples were collected for ethinyl estradiol PK at the preset time points described in the Time Frame. AUCinf calculated area under the plasma concentration-time profile from time 0 extrapolated to infinite time.

  For Part B Periods 1, 3, 5: At 0 (prior to EE dose), 0.5, 1, 1.5, 2, 4, 8, 12, 24, 48, 72, 96, 120 hours post EE dose on Day 1 in Periods 1, 3, 5 of each period.

Secondary Outcomes (14)

• (Part A) Number of Participants With Treatment Emergent Adverse Events (TEAE) During Part A of the Study

  From Baseline up to follow-up telephone contact (Days 90-97) in Part A of the study.

• (Part B) Number of Participants With TEAE During Part B of the Study

  From Baseline up to follow-up telephone contact (Days 94-101) in Part B of the study.

• (Part A) Number of Participants With Clinical Laboratory Abnormalities During Part A of the Study (Without Regard to Baseline Abnormality)

  From Baseline up to follow-up visit (Days 69-72) in Part A of the study.

• (Part B) Number of Participants With Clinical Laboratory Abnormalities During Part B of the Study (Without Regard to Baseline Abnormality)

  From Baseline up to follow-up visit (Days 72-75) in Part B of the study.

• (Part A) Number of Participants With Vital Signs Abnormalities During Part A of the Study

  From Baseline up to follow-up visit (Days 69-72) in Part A of the study.

Study Arms (2)

Part A

EXPERIMENTAL

To evaluate the effect of 2 steady-state dose levels of PF-06882961 on the Single Dose pharmacokinetics of atorvastatin (20 mg tablet) and midazolam (5 mg syrup).

Drug: PF-06882961; Drug: Atorvastatin; Drug: Midazolam

Part B

EXPERIMENTAL

To evaluate the effect of 2 steady-state dose levels of PF-06882961 on the Single Dose pharmacokinetics of an Oral Contraceptive (Levonorgestrel 0.15 mg and Ethinyl Estradiol 0.03 mg tablet).

Drug: PF-06882961; Drug: Levonorgestrel & Ethinyl Estradiol

Interventions

PF-06882961 DRUG

Tablets

Part A; Part B

Atorvastatin DRUG

Tablets

Part A

Midazolam DRUG

Syrup

Part A

Levonorgestrel & Ethinyl Estradiol DRUG

Tablet

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:

• Part A Only - Healthy male and female participants must be 18 to 65 years of age, inclusive, at the time of signing the ICD (healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, physical examination, including blood pressure and pulse rate measurement, standard 12 lead ECG and clinical laboratory tests).
• Part B Only - Healthy PM female participants between 40 and 65 years of age, inclusive, at the time of signing the ICD (healthy is defined as no clinically relevant abnormalities identified by a detailed medical history, physical examination, including BP and PR measurement, standard 12 lead ECG and clinical laboratory tests). Subjects must be amenorrheic for at least 12 months. Women who are 60 years of age or younger must also have an FSH that is within the laboratory's reference range for PM women.
• Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
• BMI- 20.0 kg/m2 to \<30.0 kg/m2 at Screening.
• Stable body weight, defined as \<5 % change (per participant report) for 90 days before Screening.
• Capable of giving signed informed consent as described in Appendix 1, 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, prior bariatric surgery, gastrectomy, or any area of intestinal resection, active inflammatory bowel disease or pancreatic insufficiency).
• Other medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality 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-1R agonists.
• Known hypersensitivity to atorvastatin or midazolam (for participants in Part A), or LE and EE (for participants in Part B).
• Personal or family history of MTC or MEN2 or study participants with suspected MTC per the investigator's judgment.
• Symptomatic gallbladder disease.
• History of major depressive disorder or history of other severe psychiatric disorders (eg, schizophrenia or bipolar disorder) within the last 2 years from screening.
• Any lifetime history of a suicide attempt.
• 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.
• Systemic therapy with any of the medications that are moderate or strong CYP3A4/5, CYP2C9 and/or CYP2C19 inhibitors within 28 days or 5 half-lives (whichever is longer) or moderate or strong CYP3A, CYP2C9 and/or CYP2C19 inducers within 28 days or 5 half-lives (whichever is longer) prior to the first dose of study intervention.
• Systemic therapy with inhibitors of the BCRP transporter within 28 days or 5 half lives (whichever is longer) prior to the first dose of study intervention.
• Current use of any prohibited concomitant medication(s) or those unwilling/unable to use a permitted concomitant medication(s).
• 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).
• Known prior participation in a trial involving PF-06882961.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

Anaheim Clinical Trials, LLC

Anaheim, California, 92801, United States

Location

Related Links

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

MeSH Terms

Interventions

danuglipron; Atorvastatin; Midazolam; Ethinyl Estradiol-Norgestrel Combination

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Ethinyl Estradiol; Norpregnatrienes; Norpregnanes; Norsteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Norgestrel; Norpregnenes; Estrogenic Steroids, Alkylated; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Limitations and Caveats

In part A, a majority of participants discontinued from study interventions due to SARS-CoV-2 infection and data from only 3 to 4 participants were evaluable following administration of danuglipron 200 mg BID. The resulting data should, therefore, be interpreted with caution.

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
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 13, 2021
• First Posted: October 26, 2021
• Study Start: October 25, 2021
• Primary Completion: July 6, 2022
• Study Completion: July 6, 2022
• Last Updated: August 19, 2024
• Results First Posted: August 19, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)