A Drug-Drug Interaction Study to Estimate the Effect of PF-07081532 on the Pharmacokinetics of Dabigatran and Rosuvastatin in Overweight or Obese Adult Participants

Healthy Clinical Trial

Official title:

A PHASE 1, OPEN-LABEL, FIXED-SEQUENCE STUDY TO ESTIMATE THE EFFECT OF PF-07081532 ADMINISTRATION ON THE SINGLE-DOSE PHARMACOKINETICS OF DABIGATRAN AND ROSUVASTATIN IN OVERWEIGHT OR OBESE ADULT PARTICIPANTS

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05788328
• Other study ID #: C3991047
• Status: Terminated
• Phase: Phase 1
• Start date: March 27, 2023
• Est. completion date: September 11, 2023

Study information

• Verified date: October 2023
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study was to understand the effect of PF-07081532 on the movement of Dabigatran and Rosuvastatin into, though, and out of the body in healthy overweight or obese adult participants. This study also aims to collect data on safety and how tolerable the study medicine is. The study is seeking for participants who are: - Male or female who are 18 years of age or older. - Healthy but are overweight or obese. Participants will receive dabigatran and rosuvastatin as single doses by mouth 3 times during the study. The amount of the study medicine PF-07081532 will be adjusted over time until any interactions are seen. PF-07081532 is taken daily by mouth in 8 Study Periods while admitted into the study clinic over 53 days. Once discharged from the study clinic, participants will have a follow-up visit 7 to 10 days post last dose of study medicine. Then another follow-up via telephone contact, 28 to 35 days post last dose of study medicine.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: September 11, 2023
• Est. primary completion date: September 11, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

2. Diagnosis of type 1 or type 2 diabetes mellitus or secondary forms of diabetes at Screening

3. History of myocardial infarction, unstable angina, arterial revascularization, mechanical prosthetic heart valve, stroke, New York Association Functional Class II-IV heart failure, or transient ischemic attack within 6 months of Screening

4. Any malignancy not considered cured (except basal cell carcinoma and squamous cell carcinoma of the skin)

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

6. Acute pancreatitis, a history of repeated episodes of acute pancreatitis, or history of chronic pancreatitis

7. Symptomatic gallbladder disease

8. Medical history or characteristics suggestive of genetic or syndromic obesity or obesity induced by other endocrinological disorders

9. History of depressive disorder or history of other severe psychiatric disorders within the last 2 years from Screening

10. Any lifetime history of a suicide attempt

11. Known medical history of active liver disease, or prior known drug-induced liver injury

12. History of HIV infection

13. Recent history of bleeding, or risks of bleeding, or abnormal coagulation test (INR >1.3) result at Screening

14. Use of prohibited medications

15. Screening supine BP =140 mm Hg (systolic) or =90 mm Hg (diastolic), following at least 5 minutes of supine rest

16. Standard 12-lead ECG that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study result

17. Participants with clinical laboratory test abnormalities at Screening

Related Conditions & MeSH terms

• Healthy
• Overweight

Intervention

Drug:
• Dabigatran etexilate (DE)
Dabigatran etexilate (DE) as oral capsule
• Rosuvastatin
Rosuvastatin as oral tablet
• PF-07081532
PF-07081532 as oral tablets

Locations

Country	Name	City	State
United States	Qps-Mra, Llc	South Miami	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of total dabigatran [if data permits otherwise Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)]	To estimate the effect of multiple dose PF-07081532 on the single-dose of dabigatran etexilate (DE) in otherwise healthy overweight or obese participants.	0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 48 hours post dose in Periods 1, 4, and 7
Primary	Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of rosuvastatin [if data permits otherwise Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)]	To estimate the effect of multiple dose PF-07081532 on the single-dose of rosuvastatin in otherwise healthy overweight or obese participants.	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72, and 96 hours post dose in Periods 2, 5, and 8
Secondary	Percentage of participants reporting Treatment Emergent Adverse Events (TEAE)		up to 28-35 days post dose
Secondary	Percentage of participants reporting clinical laboratory abnormalities	including vital signs, body weight, and ECG parameters.	up to Day 53 (up to 7-10 days post last dose if available)
Secondary	Number of Participants responding yes to any suicidal behavior question according to Columbia-Suicide Severity Rating Scale (C-SSRS)	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.	Day -1, Day 14, Day 28, Day 42, Day 53 (at follow up 7-10 days post last dose if available)
Secondary	Number of participants with a score of =15 on Patient Health Questionnaire-9 (PHQ-9)	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.	Day -1, Day 14, Day 28, Day 42, Day 53 (at follow up 7-10 days post last dose if available)
Secondary	Maximum Observed Plasma Concentration (Cmax) of total dabigatran		0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 48 hours post dose in Periods 1, 4, and 7
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of total dabigatran		0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 48 hours post dose in Periods 1, 4, and 7
Secondary	Apparent Oral Clearance (CL/F) of total dabigatran	As data permits	0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 48 hours post dose in Periods 1, 4, and 7
Secondary	Apparent Volume of Distribution (Vz/F) of total dabigatran	As data permits	0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 48 hours post dose in Periods 1, 4, and 7
Secondary	Plasma Decay Half-Life (t1/2) of total dabigatran	As data permits	0 (pre-dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 48 hours post dose in Periods 1, 4, and 7
Secondary	Maximum Observed Plasma Concentration (Cmax) of rosuvastatin		0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72, and 96 hours post dose in Periods 2, 5, and 8
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of rosuvastatin		0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72, and 96 hours post dose in Periods 2, 5, and 8
Secondary	Apparent Oral Clearance (CL/F) of rosuvastatin	As data permits	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72, and 96 hours post dose in Periods 2, 5, and 8
Secondary	Apparent Volume of Distribution (Vz/F) of rosuvastatin	As data permits	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72, and 96 hours post dose in Periods 2, 5, and 8
Secondary	Plasma Decay Half-Life (t1/2) of rosuvastatin	As data permits	0 (pre-dose), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72, and 96 hours post dose in Periods 2, 5, and 8
Secondary	Area under the plasma concentration time-curve from zero to time 24 hours (AUC24) of PF-07081532		0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 14, and 24 hours post dose in Periods 4 and 7
Secondary	Maximum Observed Plasma Concentration (Cmax) of PF-07081532		0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 14, and 24 hours post dose in Periods 4 and 7
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax) of PF-07081532		0 (pre-dose), 0.5, 1, 2, 4, 6, 8, 10, 14, and 24 hours post dose in Periods 4 and 7

External Links

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