A Study to Learn if the Study Medicines Called Itraconazole and Cyclosporine Change How the Body Processes the Other Study Medicine Called Danuglipron in Healthy Adults.

Phase 1

Not yet recruiting

• Conditions: Healthy
• Interventions: Drug: Danuglipron; Drug: Cyclosporine; Drug: Itraconazole

• Registration Number: NCT06541678
• Lead Sponsor: Pfizer

Brief Summary

The purpose of this study is to see how single dose of cyclosporine and multiple doses of itraconazole affect the level of the study medicine danuglipron in the blood of healthy adult participants. The information from this study may inform how danuglipron will be used in the future with medicines like cyclosporine and itraconazole.

Detailed Description

This study is seeking healthy participants who:

* are aged 18 years of age or older.

* are confirmed to be healthy by some medical tests.

* both men and women can participate. Women who can produce a baby must agree to use a highly effective method of birth control.

* have body mass index (BMI) of 16 to 32 kilograms per meter squared.
...

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2024-08-02
• Study First Submitted QC: 2024-08-02
• Study First Posted: 2024-08-07
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-10
• Last Update Posted: 2024-10-11
• Study Start: 2024-12-16
• Primary Completion: 2025-03-14
• Study Completion: 2025-03-14

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

1. Male and female 18 years of age or older (or the minimum age of consent in accordance with local regulations) at screening who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, blood pressure, pulse rate and standard 12-lead ECG.
2. BMI of 16-32 kg/m2; and a total body weight >50 kg (110 lb).

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Exclusion Criteria

1. Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal (including acute pancreatitis or a history of chronic pancreatitis), cardiovascular, hepatic, psychiatric, neurological, or allergic disease (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at the time of dosing).

   • Any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy).
   • History of HIV infection, hepatitis B, or hepatitis C; positive testing for HIV, HBsAg, or HCVAb. Hepatitis B vaccination is allowed.
   • Known intolerance or hypersensitivity to GLP-1R agonists.
   • Known hypersensitivity to itraconazole or cyclosporine.

2. Personal or family history of MTC or MEN2, or participants with suspected MTC per the investigator's judgment.

3. Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality or other conditions that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.

   Prior/Concomitant Therapy:

4. Use of prescription or nonprescription drugs and dietary and herbal supplements within 14 days or 5 half lives (whichever is longer; 14 days plus 5 half-lives for moderate or strong CYP3A inducers) prior to the first dose of study intervention (Refer to Section 6.9 for additional details).

5. Prior or current use of any prohibited concomitant medication(s) (Refer to Section 6.9 for additional details).

   Prior/Concurrent Clinical Study Experience:

6. Previous administration of an investigational product (drug or vaccine) within 30 days or 5 half lives preceding the first dose of study intervention used in this study (whichever is longer). Participation in studies of other investigational products (drug or vaccine) at any time during participation in this study.

7. Known prior participation (ie, randomized and received at least 1 dose of investigational product) in a study involving danuglipron.

8. A positive urine drug test at Screening or Day -1.

9. Screening supine BP ≥140 mm Hg (systolic) or ≥90 mm Hg (diastolic) for participants <60 years; and ≥150/90 mm Hg for participants ≥60 years old, following at least 5 minutes of supine rest. If systolic BP is ≥140 or 150 mm Hg (based on age) or diastolic BP ≥90 mm Hg, the BP should be repeated 2 more times and the average of the 3 BP values should be used to determine the participant's eligibility.

10. An eGFR (<60 units of mL/min/1.73 m²) as determined by the CKD-EPI equation using Screat as described in Section 10.7.2.

11. Standard 12 lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results (eg, QTcF >450 ms, complete LBBB, signs of an acute or indeterminate age myocardial infarction, ST segment and/or T wave changes suggestive of myocardial ischemia, second or third degree AV block, or serious bradyarrhythmias or tachyarrhythmias). If QTcF exceeds 450 ms, or QRS exceeds 120 ms, the ECG should be repeated twice and the average of the 3 QTcF or QRS values used to determine the participant's eligibility. Computer interpreted ECGs should be overread by an investigator experienced in reading ECGs before excluding a participant.

12. Participants with ANY of the following abnormalities in clinical laboratory tests at screening, as assessed by the study specific laboratory and confirmed by a single repeat test, if deemed necessary:

    • ALT or AST ≥1.5× ULN;
    • Total bilirubin level ≥1.5 × ULN; participants with a history of Gilbert's syndrome may have direct bilirubin measured and would be eligible for this study provided the direct bilirubin level is ≤ULN;
    • Hemoglobin A1c (HbA1c) ≥6.5%;
    • Fasting blood glucose ≥126 mg/dL (7 mmol/L).

13. History of alcohol abuse or repeated binge drinking and/or any other illicit drug use or dependence within 6 months of screening.

14. Use of tobacco/nicotine containing products in excess of the equivalent of 5 cigarettes/day or 2 chews of tobacco/day.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Period 1: Danuglipron	Danuglipron	Participants will receive a single 20 mg dose of danuglipron on Day 1.
Period 2: Cyclosporine + Danuglipron	Danuglipron	Participants will receive a single 20 mg dose of danuglipron and a single 600 mg dose of cyclosporine on Day 1.
Period 2: Cyclosporine + Danuglipron	Cyclosporine	Participants will receive a single 20 mg dose of danuglipron and a single 600 mg dose of cyclosporine on Day 1.
Period 3: Itraconazole + Danuglipron	Danuglipron	Participants will receive itraconazole daily for 6 days plus a single dose of danuglipron on Day 4.
Period 3: Itraconazole + Danuglipron	Itraconazole	Participants will receive itraconazole daily for 6 days plus a single dose of danuglipron on Day 4.

Primary Outcome Measures

Name	Time	Method
AUCinf (if data permits otherwise AUClast): to estimate the effect of a single dose of cyclosporine on the single-dose PK of a MR formulation of danuglipron in healthy adult participants.	0 to 72 hour postdose	AUCinf: Area under the plasma concentration time profile from time zero extrapolated to infinite time; AUClast: Area under the plasma concentration time profile from time zero to the time of the last quantifiable concentration.
Cmax: to estimate the effect of a single dose of cyclosporine on the single-dose PK of a MR formulation of danuglipron in healthy adult participants.	0 to 72 hour postdose	Maximum observed plasma concentration
AUCinf (if data permits otherwise AUClast): to estimate the effect of multiple doses of itraconazole on the single-dose PK of a MR formulation of danuglipron in healthy adult participants.	0 to 72 hour postdose	AUCinf: Area under the plasma concentration time profile from time zero extrapolated to infinite time; AUClast: Area under the plasma concentration time profile from time zero to the time of the last quantifiable concentration.
Cmax: to estimate the effect of multiple doses of itraconazole on the single-dose PK of a MR formulation of danuglipron in healthy adult participants.	0 to 72 hour postdose	Maximum observed plasma concentration

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Treatment Emergent Adverse Events Following Single Doses of Danuglipron administered separately and in combination with itraconazole or cyclosporine	Day 1 up to approximately Day 47
Number of Participants With Clinical Laboratory Abnormalities Following Single Doses of Danuglipron administered separately and in combination with itraconazole or cyclosporine	Day 1 up to approximately Day 47
Number of Participants With Clinically Significant Change from Baseline Vital Signs Following Single Doses of Danuglipron administered separately and in combination with itraconazole or cyclosporine	Day 1 up to approximately Day 47
Number of Participants With Clinically Significant Change from Baseline in Electrocardiogram Findings Following Single Doses of Danuglipron administered separately and in combination with itraconazole or cyclosporine	Day 1 up to approximately Day 47

Trial Locations

Locations (1)

Pfizer Clinical Research Unit - Brussels; 🇧🇪 Bruxelles, Bruxelles-Capitale, Belgium