Clinical trial NCT05745701: A Drug-Drug Interaction Study to Examine the Impact of Itraconazole and Cyclosporine on PF-07081532 Pharmacokinetics in Overweight or Obese Adults
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2023-02-27
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility 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. -

Primary outcomes:
measure: Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine
timeFrame: 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:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: 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
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Baseline (pre-dose on Day 1), Period 2 Day 5 (Study Day 10), and Period 3 Day 10 (Study Day 20)
measure: Number of Participants Meeting Pre-Specified Criteria of Vital Signs
timeFrame: 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)
measure: Change From Baseline in Body Weight at the End of Periods 1, 2, and 3
timeFrame: 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)
measure: Number of Participants Meeting Pre-Specified Criteria of Electrocardiogram (ECGs)
timeFrame: 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)
measure: Number of Participants With Suicidal Ideation or Behavior According to Columbia Suicide Severity Rating Scale (C-SSRS)
timeFrame: Period 1 Day -1 (Study Day -1), Period 3 Day 10 (Study Day 20) or Early Termination visit
measure: Number of Participants With a Score of ≥15 on Patient Health Questionnaire-9 (PHQ-9)
timeFrame: Period 1 Day -1 (Study Day -1), Period 3 Day 10 (Study Day 20) or Early Termination visit
measure: Maximum Observed Plasma Concentration (Cmax) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine
timeFrame: 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.
measure: Time to Cmax (Tmax) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine
timeFrame: 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.
measure: Apparent Oral Clearance (CL/F) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine
timeFrame: 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.
measure: Apparent Oral Volume of Distribution (Vz/F) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine
timeFrame: 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.
measure: Terminal Half-life (t1/2) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine
timeFrame: 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.
Other outcomes:
Locations:
city: New Haven
country: United States
facility: New Haven Clinical Research Unit
state: Connecticut
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: