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

Pfizer

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Device: Cyclosporine; Drug: Itraconazole; Drug: PF-07081532

Study type: Interventional

Funder types: Industry

Identifiers

NCT05745701

C3991041

Details and patient eligibility

About

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.

Enrollment: 16 patients

Sex: All

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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. -

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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16 participants in 3 patient groups

Period 1: PF-07081532

Active Comparator group

Description:

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

Treatment:

Drug: PF-07081532

Period 2: Cyclosporine + PF-07081532

Experimental group

Description:

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

Treatment:

Drug: PF-07081532

Device: Cyclosporine

Period 3: Itraconazole + PF-07081532

Experimental group

Description:

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

Treatment:

Drug: PF-07081532

Drug: Itraconazole