A Drug-Drug Interaction Study to Examine the Impact of Itraconazole and Cyclosporine on PF-07081532 Pharmacokinetics in Overweight or Obese Adults
Study Details
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 |
|---|---|---|
|
Phase 1 |
Study Design
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
- 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. [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)
- 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. [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
- Percentage of participants reporting Treatment Emergent Adverse Events (TEAE) [up to 28 days]
- Percentage of participants reporting clinical laboraroy abnormalities [up to 28 days]
including vital signs, body weight, and ECG parameters.
- Number of Participants responding yes to any suicidal behavior question according to Columbia-Suicide Severity Rating Scale (C-SSRS) [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
- Number of participants with a score of ≥15 on Patient Health Questionnaire-9 (PHQ-9) [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
- Maximum Observed Plasma Concentration (Cmax) of PF-07081532 [0 (pre-dose) 0.5 1 2 4 6 8 10 12 14 24 36 48 72 96 and 120 hours post dose]
- Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07081532 [0 (pre-dose) 0.5 1 2 4 6 8 10 12 14 24 36 48 72 96 and 120 hours post dose]
- Apparent Oral Clearance (CL/F) of PF-07081532 [0 (pre-dose) 0.5 1 2 4 6 8 10 12 14 24 36 48 72 96 and 120 hours post dose]
- Apparent Volume of Distribution (Vz/F) of PF-07081532 [0 (pre-dose) 0.5 1 2 4 6 8 10 12 14 24 36 48 72 96 and 120 hours post dose]
- Plasma Decay Half-Life (t1/2 of PF-07081532 [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
Criteria
Inclusion Criteria:
-
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.
Exclusion Criteria:
-
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. -
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | New Haven Clinical Research Unit | New Haven | Connecticut | United States | 06511 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- C3991041