A Drug-Drug Interaction Study to Examine the Impact of Itraconazole and Cyclosporine on PF-07081532 Pharmacokinetics in Overweight or Obese Adults

NCT05745701 | Completed Phase 1 Results FDA Drug

• 1 other identifier: C3991041
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, open-label, fixed-sequence, 3-period study to evaluate the effect of multiple doses of itraconazole and a single dose of cyclosporine on the single-dose PK of PF-07081532 in otherwise healthy, overweight or obese, adult female and male participants. The 3 study periods will be conducted consecutively without a break.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine

  AUCinf is area under the plasma concentration-time profile from time zero extrapolated to infinite time. AUCinf is caluculated by AUClast + (Clast/kel), where Clast is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.

  Pre-dose of lotiglipron and at 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, and 144 (for Period 3 only) hours post dose of lotiglipron on Day 1 of Periods 1 and 2 and on Day 4 of Period 3.

Secondary Outcomes (12)

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

  From the first dose up to 35 days after administration of the final dose of study intervention (Period 3 Day 9, Study Day 19), the maximum duration was 54 Days

• Number of Participants With Laboratory Abnormalities

  Baseline (pre-dose on Day 1), Period 2 Day 5 (Study Day 10), and Period 3 Day 10 (Study Day 20)

• Number of Participants Meeting Pre-Specified Criteria of Vital Signs

  Pre-dose Day 1 in periods 1, 2 and 3 (Study Days 1, 6, and 11, respectively), and prior to discharge on Period 3 Day 10 (Study Day 20)

• Change From Baseline in Body Weight at the End of Periods 1, 2, and 3

  Baseline (pre-dose on Day 1), Day 5 of Period 1 (Study Day 5), Day 5 of Period 2 (Study Day 10), and Day 10 of Period 3 (Study Day 20)

• Number of Participants Meeting Pre-Specified Criteria of Electrocardiogram (ECGs)

  Pre-dose Day 1 in periods 1, 2 and 3 (Study Days 1, 6, and 11, respectively), and prior to discharge on Period 3 Day 10 (Study Day 20)

Study Arms (3)

Period 1: PF-07081532

ACTIVE COMPARATOR

Participants will receive PF-07081532 as a single dose on Day 1.

Drug: PF-07081532

Period 2: Cyclosporine + PF-07081532

EXPERIMENTAL

Participants will receive a single dose of PF-07081532 and a single dose of cyclosporine on Day 1.

Drug: PF-07081532; Device: Cyclosporine

Period 3: Itraconazole + PF-07081532

EXPERIMENTAL

Participants will receive itraconazole daily for 9 days plus a single dose of PF-07081532 on Day 4.

Drug: PF-07081532; Drug: Itraconazole

Interventions

PF-07081532 DRUG

Oral Tablet

Period 1: PF-07081532; Period 2: Cyclosporine + PF-07081532; Period 3: Itraconazole + PF-07081532

Cyclosporine DEVICE

Oral Solution

Period 2: Cyclosporine + PF-07081532

Itraconazole DRUG

Oral Capsule

Period 3: Itraconazole + PF-07081532

Eligibility Criteria

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

You may qualify if:

• Otherwise healthy female and male participants must be at least 18 years of age 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).
• BMI: ≥25.0 kg/m2 at Screening.
• Stable body weight, defined as \<5 kg change (per participant report) for 90 days before Screening.

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).
• Diagnosis of type 1 or type 2 diabetes mellitus or secondary forms of diabetes at Screening.
• Any malignancy not considered cured (except basal cell carcinoma and squamous cell carcinoma of the skin)
• Personal or family history of MTC or MEN2, or study participants with suspected MTC per the investigator's judgment.
• Acute pancreatitis, a history of repeated episodes of 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 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, including chronic 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.
• Any lifetime history of a suicide attempt.
• Use of prohibited medications
• Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest.
• Standard 12-lead ECG that demonstrates clinically relevant abnormalities that mayaffect participant safety or interpretation of study result.
• Participants with clinical laboratory test abnormalities at Screening. -

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

New Haven Clinical Research Unit

New Haven, Connecticut, 06511, United States

Location

Related Links

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

MeSH Terms

Interventions

Itraconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines

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: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2023
• First Posted: February 27, 2023
• Study Start: February 22, 2023
• Primary Completion: May 29, 2023
• Study Completion: May 29, 2023
• Last Updated: September 23, 2024
• Results First Posted: September 23, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)