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

Pfizer16 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Healthy

Interventions

PF-07081532DRUG

Oral Tablet

CyclosporineDEVICE

Oral Solution

ItraconazoleDRUG

Oral Capsule

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. 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). 2. BMI: ≥25.0 kg/m2 at Screening. 3. Stable body weight, defined as \<5 kg change (per participant report) for 90 days before Screening. 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. Diagnosis of type 1 or type 2 diabetes mellitus or secondary forms of diabetes at Screening. 3. Any malignancy not considered cured (except basal cell carcinoma and squamous cell carcinoma of the skin) 4. Personal or family history of MTC or MEN2, or study participants with suspected MTC per the investigator's judgment. 5. Acute pancreatitis, a history of repeated episodes of acute pancreatitis, or history of chronic pancreatitis. 6. Symptomatic gallbladder disease. 7. Medical history or characteristics suggestive of genetic or syndromic obesity or obesity induced by other endocrinological disorders (eg, Cushing Syndrome). 8. History of depressive disorder or history of other severe psychiatric disorders (eg, schizophrenia or bipolar disorder) within the last 2 years from screening. 9. 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. 10. History of HIV infection. 11. Any lifetime history of a suicide attempt. 12. Use of prohibited medications 13. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic), following at least 5 minutes of supine rest. 14. Standard 12-lead ECG that demonstrates clinically relevant abnormalities that mayaffect participant safety or interpretation of study result. 15. Participants with clinical laboratory test abnormalities at Screening. -

Locations (1)

New Haven Clinical Research Unit

New Haven, Connecticut, United States

Outcomes

Primary Outcomes

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.

Time frame: 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

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

An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) was defined as an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. Any AEs occurring following start of treatment were considered as treatment emergent adverse event (TEAE). Events that occur during follow-up within the lag time of up to 35 days after the last dose of study intervention were counted as treatment emergent and attributed to the last treatment taken.

Time frame: 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

Participants with laboratory abnormalities (without regard to baseline abnormality) that met pre-specified criteria: For HEMATOLOGY, 1) Erythrocyte (Ery.) Mean Corpuscular Volume (fL) \< 0.9\*Lower limit of normal (LLN), 2) Ery. Mean Corpuscular Hemoglobin (picograms \[pg\]/cell) \< 0.9\*LLN; 3） Eosinophils/Leukocytes (%)\> 1.2\*upper limit of normal (ULN); for CLINICAL CHEMISTRY, Urate (mg/dL)\> 1.2\*ULN; for URINALYSIS, Urine Hemoglobin (Scalar)≥ 1.

Data from ClinicalTrials.gov

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