HealthyPhase 1NCT05788328

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

A Phase 1 study testing Dabigatran etexilate (DE), Rosuvastatin and PF-07081532 in people with Healthy, run by Pfizer at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

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. Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Healthy
What is being tested?: Dabigatran etexilate (DE), Rosuvastatin and PF-07081532
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 16 participants
Where: 1 siteUnited States
Study dates: 27 Mar 2023to 11 Sep 2023
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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

Who cannot join

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease
Diagnosis of type 1 or type 2 diabetes mellitus or secondary forms of diabetes at Screening
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
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

Show all 17Show fewer

Symptomatic gallbladder disease
Medical history or characteristics suggestive of genetic or syndromic obesity or obesity induced by other endocrinological disorders
History of depressive disorder or history of other severe psychiatric disorders within the last 2 years from Screening
Any lifetime history of a suicide attempt
Known medical history of active liver disease, or prior known drug-induced liver injury
History of HIV infection
Recent history of bleeding, or risks of bleeding, or abnormal coagulation test (INR >1.3) result at Screening
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 may affect participant safety or interpretation of study result
Participants with clinical laboratory test abnormalities at Screening

Trial locations and contacts

1 site in 1 country.

United States1 site

Qps-Mra, Llc
South Miami, Florida, 33143

Other trials in United States

About this study

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

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.

Conditions: Healthy
Being tested: Dabigatran etexilate (DE), Rosuvastatin, PF-07081532
Keywords: Dabigatran etexitlate, Rosuvastatin, Molecular Mechanisms of Pharmacological Action, Physiological Effects of Drugs, BCRP substrate, P-gp substrate, Anticoagulant, Antihyperlipidemic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Dabigatran etexilate (DE)Drug
Also called Pradaxa
Dabigatran etexilate (DE) as oral capsule
RosuvastatinDrug
Also called Crestor
Rosuvastatin as oral tablet
PF-07081532Drug
Also called Lotiglipron
PF-07081532 as oral tablets

Study groups in NCT05788328
Study group	Role	What they receive
Period 1	Active comparator	Participants will receive dabagatrin etexilate (DE) as a single dose Receives: Drug: Dabigatran etexilate (DE)
Period 2	Active comparator	Participants will receive rosuvastatin as a single dose Receives: Drug: Rosuvastatin
Period 3	Active comparator	Participants will receive PF-07081532 daily titrated Receives: Drug: PF-07081532
Period 4	Experimental	Participants will receive PF-07081532 daily and DE as a single dose Receives: Drug: Dabigatran etexilate (DE); Drug: PF-07081532
Period 5	Experimental	Participants will receive PF-07081532 daily and rosuvastatin as a single dose Receives: Drug: Rosuvastatin; Drug: PF-07081532
Period 6	Active comparator	Participants will receive PF-07081532 daily titrated Receives: Drug: PF-07081532
Period 7	Experimental	Participants will receive PF-07081532 daily and DE as a single dose Receives: Drug: Dabigatran etexilate (DE); Drug: PF-07081532
Period 8	Experimental	Participants will receive PF-07081532 daily and rosuvastatin as a single dose Receives: Drug: Rosuvastatin; Drug: PF-07081532

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Concentration-Time Curve From Time Zero (0) Extrapolated to Infinity (AUCinf) of Total Dabigatran in Period 1, 4 and 7
AUCinf was calculated as AUClast + (Clast/kel), where AUClast is area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast), Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel is first-order elimination rate constant.
Measured: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7
Area Under the Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUClast) of Total Dabigatran in Period 1, 4 and 7
AUClast was determined using the linear/log trapezoidal method.
Measured: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7
AUCinf of Rosuvastatin in Period 2, 5 and 8
AUCinf was calculated as AUClast + (Clast/kel), where AUClast is area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast), Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel is first-order elimination rate constant.
Measured: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8
AUClast of Rosuvastatin in Period 2, 5 and 8
AUClast was determined using the linear/log trapezoidal method.
Measured: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8

Secondary outcomes (20)

Number of Participants With Treatment Emergent Adverse Events (TEAEs)- All Causalities
An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. TEAEs were any untoward medical incidence in a participant during administered study intervention, whether or not these events are related to study intervention. AEs included both serious adverse events (SAEs) and all non-SAEs. An SAE was any untoward medical occurrence at any dose that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity and lastly causes a congenital anomaly/birth defect.
Measured: From first dose of study drug up to 28-35 days post last dose of study intervention (maximum up to 76-83 days)
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
The following laboratory parameters were assessed according to pre-specified criteria for abnormalities: a) hematology; erythrocytes mean corpuscular hemoglobin (picograms per cells ([pg/cells]) (less than[<]0.9*lower limit of normal [LLN]), eosinophils (10^9/Liter [L]), (more than[>]1.2*upper limit of normal [ULN]), prothrombin time (seconds)(>1.1*ULN), prothrombin international normalized ratio(>1.1*ULN); b) clinical chemistry; direct bilirubin(milligram per deciliter [mg/dL])(>1.5*ULN), aspartate aminotransferase(units per litre [U/L]) (>3.0*ULN), alanine aminotransferase(U/L)(> 3.0*ULN), gamma glutamyl transferase(U/L)(> 3.0*ULN), urate (mg/dL)(> 1.2*ULN), high density lipoprotein(HDL) cholesterol (mg/dl)(<0.8*LLN) and lipase(U/L)(> 1.5*ULN). Number of participants with any laboratory abnormalities (without regard to baseline abnormality) meeting pre-specified criteria are reported in this outcome measure.
Measured: During treatment of the study (maximum up to 48 days)
Number of Participants With Clinically Significant Vital Signs
Vital signs measurement included blood pressure (systolic blood pressure [SBP], diastolic blood pressure [DBP] and pulse rate (PR) and were measured in a supine position after approximately 5 minutes of rest for the participant. Clinical significance in vital signs was judged by investigator.
Measured: From first dose of study drug up to 28-35 days post last dose of study intervention (maximum up to 76-83 days)
Percent Change From Baseline in Body Weight
Measured: Baseline, Day 1 and 8 of Period 3, Day 1 of Period 5, Day 5 and 12 of Period 6, Day 1 and 5 of Period 8 and follow-up (28-35 days post last dose; up to 76 to 83 days)
Number of Participants With Pre-defined Criteria of Electrocardiogram (ECG) Parameters
Pre-defined criteria for ECG abnormalities included: PR interval aggregate (millisecond [msec], max. >=300; baseline > 200 and max. increase >= 25 percent (%); baseline > 200 and max. increase >= 25%), QRS interval (msec, max >=140; max. increase >= 50%), QT interval correct by Frederica formula (QTCF) interval aggregate (msec, 450 < max <= 480; 480 < max. <= 500; max. > 500; 30 < max. increase <= 60; max. increase > 60). Number of participants with at least 1 ECG abnormality are reported in this outcome measure.
Measured: From first dose of study drug up to 28-35 days post last dose of study intervention (maximum up to 76-83 days)
Number of Participants 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. Yes/No responses are mapped to Columbia classification algorithm of suicide assessment (C-CASA) categories: completed suicide, suicide attempt, preparatory acts toward imminent suicidal behavior, suicidal ideation, and self-injurious behavior, or no suicidal intent. n this outcome measure, number of participants with positive response (response of "yes") for each of the five categories are reported.
Measured: From first dose of study drug up to 28-35 days post last dose of study intervention (maximum up to 76-83 days)
Number of Participants According to Patient Health Questionnaire-9 (PHQ-9) Classification
The PHQ-9 is a 9 item self-report scale for the assessment of depressive symptoms. The questions included "little interest/pleasure in things", "feeling down depressed or hopeless", "trouble falling or staying asleep", "feeling tired or little energy", "poor appetite or overeating", "feeling bad about yourself", "trouble concentrating on things", "moving slowly or fidgety/restless" and "thoughts you be better off dead". Each item was scored on scale of "not at all" (0), "several days" (1), "more than half the days" (2) to "nearly every day" (3). Total score was obtained by addition of scores for each item and resulted into overall possible score range of 0-27. Higher score = greater severity.
Measured: Day 1 prior to treatment (Day -1) in Period 1; Day 8 of Period 3; Days 5 of Period 6; Day 1 and 5 of Period 8; Follow-up: up to 53 to 56 days post last dose of study intervention
Maximum Observed Concentration (Cmax) of Total Dabigatran in Period 1, 4 and 7
Measured: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7
Time for Cmax (Tmax) of Total Dabigatran in Period 1, 4 and 7
Measured: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7
Terminal Half-Life (t1/2) of Total Dabigatran in Period 1, 4 and 7
T1/2 was calculated as loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Measured: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7
Apparent Volume of Distribution (Vz/F) of Total Dabigatran in Period 1, 4 and 7
Vz/F was calculated as dose/(AUCinf*kel). AUCinf was calculated as AUClast + (Clast/kel), where AUClast is area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast), Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel is first-order elimination rate constant.
Measured: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7
Apparent Oral Clearance (CL/F) of Total Dabigatran in Period 1, 4 and 7
CL/F was calculated as dose/AUCinf. AUCinf was calculated as AUClast + (Clast/kel), where AUClast is area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast), Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel is first-order elimination rate constant.
Measured: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7
Cmax of Rosuvastatin in Period 2, 5 and 8
Measured: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8
Tmax of Rosuvastatin in Period 2, 5 and 8
Measured: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8
t1/2 of Rosuvastatin in Period 2, 5 and 8
T1/2 was calculated as loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve.
Measured: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8
Vz/F of Rosuvastatin in Period 2, 5 and 8
Vz/F was calculated as dose/(AUCinf*kel). AUCinf was calculated as AUClast + (Clast/kel), where AUClast is area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast), Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel is first-order elimination rate constant.
Measured: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8
CL/F of Rosuvastatin in Period 2, 5 and 8
CL/F was calculated as dose/AUCinf. AUCinf was calculated as AUClast + (Clast/kel), where AUClast is area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast), Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel is first-order elimination rate constant.
Measured: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8
Area Under the Concentration-Time Curve From Time 0 to Time 24 Hours (AUC24) of PF-07081532 When Co-administered With DE and ROSU in Period 4 and 8 Respectively
Measured: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 14 and 24 hours post dose of PF-07081532 in Period 4 and 8
Cmax of PF-07081532 When Co-administered With DE and ROSU in Period 4 and 8 Respectively
Measured: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 14 and 24 hours post dose of PF-07081532 in Period 4 and 8
Tmax of PF-07081532 When Co-administered With DE and ROSU in Period 4 and 8 Respectively
Measured: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 14 and 24 hours post dose of PF-07081532 in Period 4 and 8

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Mar 202311 Sep 2023

First posted28 Mar 2023
Study start27 Mar 2023
Primary completion11 Sep 2023
Study completion11 Sep 2023

Why it stopped: The decision to terminate clinical development of lotiglipron is based on pharmacokinetic data from Phase 1 drug-drug-interaction studies and laboratory measurements of elevated transaminases in these Phase 1 studies as well as a Phase 2 study.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HealthyStudies of the same condition, open and under way.
More trials run by PfizerThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Enrolment: 16 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05788328
Sponsor's protocol ID: C3991047
Status last verified: Sep 2024
First submitted: 15 Mar 2023
Last updated: 15 Nov 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: 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.

Publications

Cronenberger C, Amin NB, Le VH, Carvajal-Gonzalez S, Ashworth AL, Yi EC, Schuster T, Zhang Y, Frederich RC, Friedman GS, Wang EQ, Tsamandouras N. Assessment of the Drug-Drug Interaction Potential of Lotiglipron (PF-07081532) with Midazolam, Omeprazole, Dabigatran, Rosuvastatin, and the Oral Contraceptives Levonorgestrel and Ethinyl Estradiol. J Clin Pharmacol. 2026 May;66(5):e70158. doi: 10.1002/jcph.70158.
PubMed 42053447

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis

All Healthy trials

Study at a glance

From the registry record, last updated by the sponsor on 15 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT05788328
Acronym / sponsor ID: C3991047
Conditions: Healthy
Keywords: Dabigatran etexitlate, Rosuvastatin, Molecular Mechanisms of Pharmacological Action, Physiological Effects of Drugs, BCRP substrate, P-gp substrate, Anticoagulant, Antihyperlipidemic
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: The decision to terminate clinical development of lotiglipron is based on pharmacokinetic data from Phase 1 drug-drug-interaction studies and laboratory measurements of elevated transaminases in these Phase 1 studies as well as a Phase 2 study.
Enrolment: 16 participants (actual)
Lead sponsor: PfizerIndustry (pharma, biotech, devices)
Study start: 27 Mar 2023 (actual)
Primary completion: 11 Sep 2023 (actual)
Study completion: 11 Sep 2023 (actual)
First posted: 28 Mar 2023 (actual)
Results: Posted 15 Nov 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: None (open label)
Number of arms: 8

Arm	Type	Receives
Period 1	Active comparator	Drug: Dabigatran etexilate (DE)Participants will receive dabagatrin etexilate (DE) as a single dose
Period 2	Active comparator	Drug: RosuvastatinParticipants will receive rosuvastatin as a single dose
Period 3	Active comparator	Drug: PF-07081532Participants will receive PF-07081532 daily titrated
Period 4	Experimental	Drug: Dabigatran etexilate (DE), Drug: PF-07081532Participants will receive PF-07081532 daily and DE as a single dose
Period 5	Experimental	Drug: Rosuvastatin, Drug: PF-07081532Participants will receive PF-07081532 daily and rosuvastatin as a single dose
Period 6	Active comparator	Drug: PF-07081532Participants will receive PF-07081532 daily titrated
Period 7	Experimental	Drug: Dabigatran etexilate (DE), Drug: PF-07081532Participants will receive PF-07081532 daily and DE as a single dose
Period 8	Experimental	Drug: Rosuvastatin, Drug: PF-07081532Participants will receive PF-07081532 daily and rosuvastatin as a single dose

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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

Key exclusion criteria (17 listed)

Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurological, or allergic disease
Diagnosis of type 1 or type 2 diabetes mellitus or secondary forms of diabetes at Screening
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
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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Dabigatran etexilate (DE)Also: PradaxaDabigatran etexilate (DE) as oral capsule	Drug	Period 1, Period 4, Period 7
RosuvastatinAlso: CrestorRosuvastatin as oral tablet	Drug	Period 2, Period 5, Period 8
PF-07081532Also: LotiglipronPF-07081532 as oral tablets	Drug	Period 3, Period 4, Period 5, Period 6, Period 7, Period 8

Primary outcome

Area Under the Concentration-Time Curve From Time Zero (0) Extrapolated to Infinity (AUCinf) of Total Dabigatran in Period 1, 4 and 7
Time frame: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7
AUCinf was calculated as AUClast + (Clast/kel), where AUClast is area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast), Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel is first-order elimination rate constant.
Area Under the Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUClast) of Total Dabigatran in Period 1, 4 and 7
Time frame: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7
AUClast was determined using the linear/log trapezoidal method.
AUCinf of Rosuvastatin in Period 2, 5 and 8
Time frame: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8
AUCinf was calculated as AUClast + (Clast/kel), where AUClast is area under the plasma concentration-time profile from time zero to the time of the last quantifiable concentration (Clast), Clast is the predicted plasma concentration at the last quantifiable time point from the log-linear regression analysis and kel is first-order elimination rate constant.
AUClast of Rosuvastatin in Period 2, 5 and 8
Time frame: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8
AUClast was determined using the linear/log trapezoidal method.

20 secondary outcomes

Number of Participants With Treatment Emergent Adverse Events (TEAEs)- All Causalities
Time frame: From first dose of study drug up to 28-35 days post last dose of study intervention (maximum up to 76-83 days)
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Time frame: During treatment of the study (maximum up to 48 days)
Number of Participants With Clinically Significant Vital Signs
Time frame: From first dose of study drug up to 28-35 days post last dose of study intervention (maximum up to 76-83 days)
Percent Change From Baseline in Body Weight
Time frame: Baseline, Day 1 and 8 of Period 3, Day 1 of Period 5, Day 5 and 12 of Period 6, Day 1 and 5 of Period 8 and follow-up (28-35 days post last dose; up to 76 to 83 days)
Number of Participants With Pre-defined Criteria of Electrocardiogram (ECG) Parameters
Time frame: From first dose of study drug up to 28-35 days post last dose of study intervention (maximum up to 76-83 days)
Number of Participants According to Columbia-Suicide Severity Rating Scale (C-SSRS)
Time frame: From first dose of study drug up to 28-35 days post last dose of study intervention (maximum up to 76-83 days)
Number of Participants According to Patient Health Questionnaire-9 (PHQ-9) Classification
Time frame: Day 1 prior to treatment (Day -1) in Period 1; Day 8 of Period 3; Days 5 of Period 6; Day 1 and 5 of Period 8; Follow-up: up to 53 to 56 days post last dose of study intervention
Maximum Observed Concentration (Cmax) of Total Dabigatran in Period 1, 4 and 7
Time frame: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7
Time for Cmax (Tmax) of Total Dabigatran in Period 1, 4 and 7
Time frame: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7
Terminal Half-Life (t1/2) of Total Dabigatran in Period 1, 4 and 7
Time frame: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7
Apparent Volume of Distribution (Vz/F) of Total Dabigatran in Period 1, 4 and 7
Time frame: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7
Apparent Oral Clearance (CL/F) of Total Dabigatran in Period 1, 4 and 7
Time frame: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7
Cmax of Rosuvastatin in Period 2, 5 and 8
Time frame: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8
Tmax of Rosuvastatin in Period 2, 5 and 8
Time frame: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8
t1/2 of Rosuvastatin in Period 2, 5 and 8
Time frame: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8
Vz/F of Rosuvastatin in Period 2, 5 and 8
Time frame: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8
CL/F of Rosuvastatin in Period 2, 5 and 8
Time frame: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8
Area Under the Concentration-Time Curve From Time 0 to Time 24 Hours (AUC24) of PF-07081532 When Co-administered With DE and ROSU in Period 4 and 8 Respectively
Time frame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 14 and 24 hours post dose of PF-07081532 in Period 4 and 8
Cmax of PF-07081532 When Co-administered With DE and ROSU in Period 4 and 8 Respectively
Time frame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 14 and 24 hours post dose of PF-07081532 in Period 4 and 8
Tmax of PF-07081532 When Co-administered With DE and ROSU in Period 4 and 8 Respectively
Time frame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 14 and 24 hours post dose of PF-07081532 in Period 4 and 8

Results and safety

Results posted to the registry on 15 Nov 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
All Participants	16	16

Primary outcome: Area Under the Concentration-Time Curve From Time Zero (0) Extrapolated to Infinity (AUCinf) of Total Dabigatran in Period 1, 4 and 7

Time frame: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7. Geometric mean (Geometric Coefficient of Variation). Unit: nanogram*hour/milliliter (ng*hr/mL)

Measure	Period 1: DE 150 mg n = 16	Period 4: DE 150 mg + PF-07081532 80 mg QD n = 15	Period 7: PF-07081532 240 mg QD + DE 150 mg n = 15
Value	1359 (43)	1195 (38)	1141 (92)

Period 1: DE 150 mg vs Period 4: DE 150 mg + PF-07081532 80 mg QD: Ratio of Adjusted Geometric Means: 86.50 (90% CI 66.05 to 113.29)
Period 1: DE 150 mg vs Period 7: PF-07081532 240 mg QD + DE 150 mg: Ratio of Adjusted Geometric Means: 82.64 (90% CI 63.10 to 108.24)

Population analysed: Pharmacokinetic (PK) parameter set included all participants who received at least 1 dose of rosuvastatin, dabigatran etexilate, and/or PF-07081532 and had at least 1 of the PK parameters of interest calculated. Here, "Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure. Data for this outcome measure was planned to be collected for Period 1, 4 and 7 only.

Primary outcome: Area Under the Concentration-Time Curve From Time 0 to the Last Measurable Concentration (AUClast) of Total Dabigatran in Period 1, 4 and 7

Time frame: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7. Geometric mean (Geometric Coefficient of Variation). Unit: ng*hr/mL

Measure	Period 1: DE 150 mg n = 16	Period 4: DE 150 mg + PF-07081532 80 mg QD n = 15	Period 7: PF-07081532 240 mg QD + DE 150 mg n = 15
Value	1326 (44)	1154 (39)	1089 (97)

Period 1: DE 150 mg vs Period 4: DE 150 mg + PF-07081532 80 mg QD: Ratio of Adjusted Geometric Means: 85.65 (90% CI 64.96 to 112.94)
Period 1: DE 150 mg vs Period 7: PF-07081532 240 mg QD + DE 150 mg: Ratio of Adjusted Geometric Means: 80.81 (90% CI 61.28 to 106.55)

Population analysed: PK parameter set included all participants who received at least 1 dose of rosuvastatin, dabigatran etexilate, and/or PF-07081532 and had at least 1 of the PK parameters of interest calculated. Here, "Number of Participants Analyzed" signifies number of participants evaluable for this outcome measure. Data for this outcome measure was planned to be collected for Period 1, 4 and 7 only.

Primary outcome: AUCinf of Rosuvastatin in Period 2, 5 and 8

Time frame: Pre-dose (0 hour), 1, 2, 3, 4, 5, 6, 8, 10, 14, 24, 48, 72 and 96 hours post dose of ROSU on Day 1 of Period 2, 5 and 8. Geometric mean (Geometric Coefficient of Variation). Unit: ng*hr/mL

Measure	Period 2: ROSU 10 mg n = 12	Period 5: ROSU 10mg + PF-07081532 80 mg QD n = 14	Period 8: PF-07081532 240 mg QD + ROSU 10 mg n = 13
Value	26.86 (36)	67.79 (58)	63.83 (60)

Period 2: ROSU 10 mg vs Period 5: ROSU 10mg + PF-07081532 80 mg QD: Ratio of Adjusted Geometric Means: 229.11 (90% CI 185.23 to 283.37)
Period 2: ROSU 10 mg vs Period 8: PF-07081532 240 mg QD + ROSU 10 mg: Ratio of Adjusted Geometric Means: 214.73 (90% CI 173.38 to 265.94)

Primary outcome: AUClast of Rosuvastatin in Period 2, 5 and 8

Measure	Period 2: ROSU 10 mg n = 16	Period 5: ROSU 10mg + PF-07081532 80 mg QD n = 15	Period 8: PF-07081532 240 mg QD + ROSU 10 mg n = 15
Value	29.69 (47)	63.30 (58)	69.03 (68)

Period 2: ROSU 10 mg vs Period 5: ROSU 10mg + PF-07081532 80 mg QD: Ratio of Adjusted Geometric Means: 213.05 (90% CI 170.46 to 266.29)
Period 2: ROSU 10 mg vs Period 8: PF-07081532 240 mg QD + ROSU 10 mg: Ratio of Adjusted Geometric Means: 232.32 (90% CI 185.88 to 290.38)

20 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose of study drug up to 28-35 days post last dose of study intervention (maximum up to 76-83 days). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Period 1: DE 150 mg	0 of 16 (0%)	0 of 16 (0%)	0 of 16
Period 2: ROSU 10 mg	0 of 16 (0%)	0 of 16 (0%)	0 of 16
Period 3: PF-07081532 40 mg QD	0 of 16 (0%)	6 of 16 (37.5%)	0 of 16
Period 4: DE 150 mg + PF-07081532 80 mg QD	0 of 16 (0%)	15 of 16 (93.8%)	0 of 16
Period 5: ROSU 10mg + PF-07081532 80 mg QD	0 of 15 (0%)	6 of 15 (40%)	0 of 15
Period 6: PF-07081532 240 mg QD	0 of 15 (0%)	15 of 15 (100%)	0 of 15
Period 7: PF-07081532 240 mg QD + DE 150 mg	0 of 15 (0%)	4 of 15 (26.7%)	0 of 15
Period 8: PF-07081532 240 mg QD + ROSU 10 mg	1 of 15 (6.7%)	9 of 15 (60%)	0 of 15

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42053447Cronenberger C, Amin NB, Le VH, Carvajal-Gonzalez S, Ashworth AL, Yi EC, Schuster T, Zhang Y, Frederich RC, Friedman GS, Wang EQ, Tsamandouras N. Assessment of the Drug-Drug Interaction Potential of Lotiglipron (PF-07081532) with Midazolam, Omeprazole, Dabigatran, Rosuvastatin, and the Oral Contraceptives Levonorgestrel and Ethinyl Estradiol. J Clin Pharmacol. 2026 May;66(5):e70158. doi: 10.1002/jcph.70158.
To obtain contact information for a study center near you, click here.Link provided by the sponsor.
Individual participant dataSharing planned: No. 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.

Related trials for Healthy

Recruiting
THE EFFECTS OF GAME-BASED EXERCISE PROGRAMS
Physical Activity, Body Image
Not yet recruitingPhase 1
A Phase I Study of GLR2053 Tablets in Chinese Healthy Adult Participants
Atopic Dermatitis
Recruiting
Colon-delivered Riboflavin and Gut Microbiota Composition
Microbiome Dysbiosis, Gut Health
Not yet recruiting
Neuroergonomic Analysis of a Brain-Computer Interface Device (BCI)
Healthy Volunteers - Male and Female
RecruitingPhase 1
First-in-Human Trial to Assess REGN20423 in Healthy Adult Participants and Adult Participants With Atopic Dermatitis
Healthy Volunteer, Atopic Dermatitis

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Pfizer CT.gov Call Center study director

Pfizer

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Dabigatran etexilate (DE), Rosuvastatin and PF-07081532 in people with Healthy, run by Pfizer at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area Under the Concentration-Time Curve From Time Zero (0) Extrapolated to Infinity (AUCinf) of Total Dabigatran in Period 1, 4 and 7 (time frame: Pre-dose (0 hour), 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose of DE on Day 1 of Period 1, 4 and 7). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05788328, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2024.