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

• ClinicalTrials.gov Identifier: NCT05745701
• Recruitment Status: Recruiting
• First Posted: February 27, 2023
• Last Update Posted: March 6, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: PF-07081532; Device: Cyclosporine; Drug: Itraconazole	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE STUDY TO EVALUATE THE EFFECT OF ITRACONAZOLE AND CYCLOSPORINE ON THE SINGLE-DOSE PHARMACOKINETICS OF PF-07081532 IN OVERWEIGHT OR OBESE ADULT PARTICIPANTS
• Actual Study Start Date: February 22, 2023
• Estimated Primary Completion Date: May 28, 2023
• Estimated Study Completion Date: May 28, 2023

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Period 1: PF-07081532; Participants will receive PF-07081532 as a single dose on Day 1.	Drug: PF-07081532; Oral Tablet
Experimental: Period 2: Cyclosporine + PF-07081532; Participants will receive a single dose of PF-07081532 and a single dose of cyclosporine on Day 1.	Drug: PF-07081532; Oral Tablet; Device: Cyclosporine; Oral Solution
Experimental: Period 3: Itraconazole + PF-07081532; Participants will receive itraconazole daily for 9 days plus a single dose of PF-07081532 on Day 4.	Drug: PF-07081532; Oral Tablet; Drug: Itraconazole; Oral Capsule

Outcome Measures

Primary Outcome Measures :

1. AUCinf (if data permits otherwise AUClast): To estimate the effect of muliple dose itraconazole on thes single dose of PF-07081532 in otherwise healthy, overweight or obese participants. [ Time Frame: 0 (pre-dose) 0.5 1 2 4 6 8 10 12 14 24 36 48 72 96 and 120 hours post dose ]

   Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)

   Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

2. AUCinf (if data permita otherwise AUClast): To estimate the effect of single dose of cyclosporine on the single dose of PF-07081532 in otherwise healthy, overweight or obese participants. [ Time Frame: 0 (pre-dose) 0.5 1 2 4 6 8 10 12 14 24 36 48 72 96 and 120 hours post dose ]

   Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf)

   Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)

Secondary Outcome Measures :

1. Percentage of participants reporting Treatment Emergent Adverse Events (TEAE) [ Time Frame: up to 28 days ]
2. Percentage of participants reporting clinical laboraroy abnormalities [ Time Frame: up to 28 days ]
   including vital signs, body weight, and ECG parameters.
3. Number of Participants responding yes to any suicidal behavior question according to Columbia-Suicide Severity Rating Scale (C-SSRS) [ Time Frame: Day 1, Day 10 or Early Termination visit ]
   The C-SSRS is an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. Participants who respond "yes" to any suicidal behavioral question on the C-SSRS will not be permitted in the study
4. Number of participants with a score of ≥15 on Patient Health Questionnaire-9 (PHQ-9) [ Time Frame: Day 1, Day 10 or Early Termination visit ]
   PHQ9-9 is a 9 item self-report scale for the assessment of depressive symptoms. A PHQ-9 score of ≥15 indicates clinically significant depression and serves as an exclusion criterion for this study
5. Maximum Observed Plasma Concentration (Cmax) of PF-07081532 [ Time Frame: 0 (pre-dose) 0.5 1 2 4 6 8 10 12 14 24 36 48 72 96 and 120 hours post dose ]
6. Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07081532 [ Time Frame: 0 (pre-dose) 0.5 1 2 4 6 8 10 12 14 24 36 48 72 96 and 120 hours post dose ]
7. Apparent Oral Clearance (CL/F) of PF-07081532 [ Time Frame: 0 (pre-dose) 0.5 1 2 4 6 8 10 12 14 24 36 48 72 96 and 120 hours post dose ]
8. Apparent Volume of Distribution (Vz/F) of PF-07081532 [ Time Frame: 0 (pre-dose) 0.5 1 2 4 6 8 10 12 14 24 36 48 72 96 and 120 hours post dose ]
9. Plasma Decay Half-Life (t1/2 of PF-07081532 [ Time Frame: 0 (pre-dose) 0.5 1 2 4 6 8 10 12 14 24 36 48 72 96 and 120 hours post dose ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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. -

Contacts and Locations

Contacts

Contact: Pfizer CT.gov Call Center; 1-800-718-1021; ClinicalTrials.gov_Inquiries@pfizer.com

Locations

United States, Connecticut

New Haven Clinical Research Unit; Recruiting

New Haven, Connecticut, United States, 06511

Sponsors and Collaborators

Pfizer

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

More Information

Additional Information:

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

• Responsible Party: Pfizer
• ClinicalTrials.gov Identifier: NCT05745701
• Other Study ID Numbers: C3991041
• First Posted: February 27, 2023
• Last Update Posted: March 6, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• 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/data_requests.

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Overweight; Overnutrition; Nutrition Disorders; Body Weight; Cyclosporine; Itraconazole; Cyclosporins; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antifungal Agents; Anti-Infective Agents; Dermatologic Agents; Antirheumatic Agents; Calcineurin Inhibitors; 14-alpha Demethylase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Steroid Synthesis Inhibitors; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Cytochrome P-450 CYP3A Inhibitors