Study To Evaluate The Effect Of Two Steady State Doses of... | NCT04621227 | Trialant
NCT04621227
Sponsor
Pfizer
Status
Completed
Last Update Posted
Dec 1, 2023Actual
Enrollment
16Actual
Phase
Phase 1
Conditions
Obesity
Interventions
PF-06882961
Rosuvastatin
Midazolam
Countries
United States
Protocol Section
Identification Module
NCT ID
NCT04621227
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
C3421007
Secondary IDs
Not provided
Brief Title
Study To Evaluate The Effect Of Two Steady State Doses of PF 06882961 On Rosuvastatin And Midazolam Pharmacokinetics In Otherwise Healthy Adult Participants With Obesity
Official Title
A PHASE 1, OPEN -LABEL, FIXED SEQUENCE STUDY TO EVALUATE THE EFFECT OF TWO STEADY STATE DOSE LEVELS OF PF-06882961 ON THE PHARMACOKINETICS OF SINGLE ORAL DOSES OF ROSUVASTATIN AND MIDAZOLAM IN OTHERWISE HEALTHY ADULT PARTICIPANTS WITH OBESITY
Acronym
Not provided
Organization
PfizerINDUSTRY
Status Module
Record Verification Date
Feb 2023
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Dec 15, 2020Actual
Primary Completion Date
May 13, 2021Actual
Completion Date
May 13, 2021Actual
First Submitted Date
Nov 3, 2020
First Submission Date that Met QC Criteria
Nov 3, 2020
First Posted Date
Nov 9, 2020Actual
Results Waived
Not provided
Results First Submitted Date
May 5, 2022
Results First Submitted that Met QC Criteria
Feb 23, 2023
Results First Posted Date
Dec 1, 2023Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Feb 23, 2023
Last Update Posted Date
Dec 1, 2023Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
PfizerINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Not provided
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
A Phase 1 Study To Evaluate The Effect Of Two Steady State Doses of PF 06882961 On Rosuvastatin And Midazolam Pharmacokinetics In Otherwise Healthy Adult Participants With Obesity
Detailed Description
This study is designed to look at the effect of two doses of PF 06882961 (120 milligram (mg) twice a day (BID) and 200 mg BID) on the levels of one dose of rosuvastatin 10 mg and one dose of midazolam 2 mg, in otherwise healthy, adult participants with obesity. Total duration of study from screening to the telephone visit will be approximately 17 weeks, of which up to 63 days will be inpatient. All subjects take (i) Rosuvastatin alone, Midazolam alone, PF 06882961 alone (120 mg BID), PF 06882961 (120 mg BID) + Rosuvastatin, PF 06882961 (120 mg BID) + Midazolam, PF 06882961 (200 mg BID) alone, PF 06882961 (200 mg BID) + Rosuvastatin, PF 06882961 (200 mg BID)+ Midazolam in the study.
Conditions Module
Conditions
Obesity
Keywords
obesity
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
16Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Period 1
Other
Participants will receive the following treatments in this sequence : (i)Rosuvastatin alone (one dose of 10 mg), (ii) Midazolam alone (one dose of 2mg), (iii) PF 06882961 alone (120 mg twice daily), (iv) PF 06882961 (120 mg twice daily) + Rosuvastatin (one dose of 10mg), (v) PF 06882961 (120 mg) + Midazolam (one dose of 2 mg), (vi) PF 06882961 (200 mg) alone, (vii) PF 06882961 (200 mg) + Rosuvastatin (one dose of 10 mg), (viii) PF 06882961 (200 mg)+ Midazolam (one dose of 2 mg) in the study.
Drug: PF-06882961
Drug: Rosuvastatin
Drug: Midazolam
Interventions
Name
Type
Description
Arm Group Labels
Other Names
PF-06882961
Drug
120 mg and 200 mg BID
Period 1
Rosuvastatin
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Area Under the Plasma Concentration-time Profile From Time 0 to Last Quantifiable Concentration (AUClast) of Rosuvastatin in Periods 1, 4 and 7
AUClast is area under the plasma concentration-time profile from time 0 to last quantifiable concentration.
At 0 (prior to rosuvastatin dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, and 72 hours post rosuvastatin dose on Day 1 in Periods 1, 4, and 7
AUClast of Midazolam in Periods 2, 5 and 8
AUClast is area under the plasma concentration-time profile from time 0 to last quantifiable concentration.
At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post midazolam dose on Day 1 in Periods 2, 5, and 8
Secondary Outcomes
Measure
Description
Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) was defined as any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect; or other serious situations such as important medical events. TEAEs were events between first dose of study drug and up to follow-up visit that were absent before treatment or that worsened after treatment. AEs presented below were TEAEs. The investigator was required to use clinical judgment to assess the potential relationship between investigational product and each AE, to define an treatment-related AE.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Body Mass Index (BMI) ≥ 30.0 kg/m2 and not more than 45.4 kg/m2 at Screening.
Stable body weight, defined as <5 kg change (per participant report) for 90 days before Screening
Exclusion Criteria:
Known prior participation in a trial involving PF-06882961.
Known intolerance or hypersensitivity to GLP-1R agonists.
Known hypersensitivity to rosuvastatin or midazolam.
Diagnosis of type 1 or type 2 diabetes mellitus or secondary forms of diabetes at screening. Note: prior diagnoses of gestational diabetes during pregnancy only are eligible if they meet the other eligibility criteria
Any lifetime history of a suicide attempt.
Blood donation (excluding plasma donations) of approximately 1 pint (500 mL) or more within 60 days prior to dosing.
Participation in a formal weight reduction program (eg, Weight Watchers) within 90 days prior to Screening.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
65 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Pfizer CT.gov Call Center
Pfizer
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Anaheim Clinical Trials, LLC
Anaheim
California
92801
United States
References Module
Citations
Not provided
See Also Links
Label
URL
To obtain contact information for a study center near you, click here.
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.
Types
Not provided
Time Frame
Not provided
Access Criteria
Not provided
URL
Not provided
Results Section
Participant Flow Module
Pre-assignment Details
Not provided
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
All Participants
Participants underwent Period 1 to 8 and received study interventions as follows: Period 1: rosuvastatin 10mg once daily (QD) on Day 1; Period 2: midazolam 2mg QD on Day 1; Period 3: PF-06882961 (danuglipron) 10mg twice a day (BID) on Days 1-4, 20mg BID on Days 5-8, 40mg BID on Days 9-12, 60mg BID on Days 13-16, 80mg BID on Days 17-20, 100mg BID on Days 21-24, and 120mg BID on Days 25-28; Period 4: PF-06882961 120mg BID on Days 1-4 + rosuvastatin 10mg QD on Day 1; Period 5: PF-06882961 120mg BID + midazolam 2mg QD on Day 1; Period 6: PF-06882961 140mg BID on Days 1-4, 160mg BID on Days 5-8, 180mg BID on Days 9-12, and 200mg BID on Days 13-16; Period 7: PF-06882961 200mg BID on Days 1-4 + rosuvastatin 10mg QD on Day 1; Period 8: PF-06882961 200mg BID + midazolam 2mg QD on Day 1.
Periods
Title
Milestones
Reasons Not Completed
Period 1 (5 Days)
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Oct 7, 2020
May 5, 2022
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
N/A
Intervention Model
Crossover Assignment
Intervention Model Description
Crossover
Primary Purpose
Other
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Drug
10 mg single dose
Period 1
Midazolam
Drug
2mg single dose
Period 1
From first dose of study drug (Day 1) to telephone Follow Up (Days 89-96) (approximately up to 96 days)
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality)
Safety laboratory assessments included clinical chemistry, hematology, urinalysis, and other tests. Abnormality was determined at the investigator's discretion.
From BL (Day 1, the last pre-dose measurement in Period 1) to Follow Up visit (Days 68-71) (approximately up to 71 days)
Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria
Single, supine vital signs assessments included systolic blood pressure (BP), diastolic BP and pulse rate. Abnormality in vital signs included: pulse rate <40 beats per minute (bpm) or >120bpm; supine diastolic BP <50 millimeter of mercury (mmHg), increase and decrease in change from BL of >=20mmHg; supine systolic blood pressure <90mmHg, increase and decrease in change from BL of >=30mmHg.
From BL (Day 1, the last pre-dose measurement in Period 1) to Follow Up visit (Days 68-71) (approximately up to 71 days)
Change From Baseline in Body Weight
Changes from Baseline in body weight of the participants were measured.
At BL (Period 1 Day 1), on Period 3 Days 1, 8, 15 and 22, Period 4 Day 1, Period 6 Days 1 and 9, Period 7 Day 1, Period 8 Day 2, and at Follow Up visit (Days 68-71)
Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria
ECG assessments included pulse rate (PR), QT, QTcF intervals and QRS complex. ECG abnormalities criteria included: PR interval value >= 300msec, or BL >200msec and >=25% increase from BL, or BL <=200msec and >=50% increase from BL; QRS interval value >= 140msec, or percent change from BL >=50%; QTcF value >400 and <=480msec, or >480 and <=500 msec, or >500msec, or change from BL>30 and <=60msec, or change from BL >60msec.
From BL (Day 1, the last pre-dose measurement in Period 1) to Follow Up visit (Days 68-71) (approximately up to 71 days)
Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS)
The C-SSRS was an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced any of the following 1: completed suicide, 2: suicide attempt (response of "yes" on "actual attempt"), 3: preparatory acts towards imminent suicidal behavior ("yes" on "aborted attempt", "interrupted attempt", "preparatory acts/behavior"), 4: suicidal ideation ("yes" on "wish to be dead", "non-specific active suicidal thoughts"), 7: self-injurious behavior, no suicidal intent ("yes" on "has participant engaged in non-suicidal self-injurious behavior"). In this outcome, number of participants with positive response (response of "yes") to suicidal behavior, ideation, or any self-injurious behavior were reported.
At BL (Period 1 Day 1), on Period 3 Days 1, 8, 15, and 22, Period 4 Day 1, Period 6 Days 1, 9, and 16, Period 8 Day 2, at Follow Up visit (Days 68-71) and Early Termination
Number of Participants With Categorical Scores on the Patient Health Questionnaire (PHQ-9)
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", "several days", "more than half the days" to "nearly every day". Total score range: 0-27 (each item with scale from 0 [not at all] to 3 [nearly every day]. Higher score=greater severity).
At BL (Period 1 Day 1), on Period 3 Days 1, 8, 15, and 22, Period 4 Day 1, Period 6 Days 1, 9, and 16, Period 8 Day 2, at Follow Up visit (Days 68-71) and Early Termination
FG00016 subjects
COMPLETED
FG00016 subjects
NOT COMPLETED
FG0000 subjects
Period 2 (2 Days)
Type
Comment
Milestone Data
STARTED
FG00016 subjects
COMPLETED
FG00016 subjects
NOT COMPLETED
FG0000 subjects
Period 3 (29 Days)
Type
Comment
Milestone Data
STARTED
FG00016 subjects
COMPLETED
FG00014 subjects
NOT COMPLETED
FG0002 subjects
Type
Comment
Reasons
Physician decision due to inappropriate behavior and noncompliance
FG0001 subjects
Adverse Event
FG0001 subjects
Period 4 (4 Days)
Type
Comment
Milestone Data
STARTED
FG00014 subjects
COMPLETED
FG00014 subjects
NOT COMPLETED
FG0000 subjects
Period 5 (1 Day)
Type
Comment
Milestone Data
STARTED
FG00014 subjects
COMPLETED
FG00014 subjects
NOT COMPLETED
FG0000 subjects
Period 6 (16 Days)
Type
Comment
Milestone Data
STARTED
FG00014 subjects
COMPLETED
FG00014 subjects
NOT COMPLETED
FG0000 subjects
Period 7 (4 Days)
Type
Comment
Milestone Data
STARTED
FG00014 subjects
COMPLETED
FG00014 subjects
NOT COMPLETED
FG0000 subjects
Period 8 (2 Days)
Type
Comment
Milestone Data
STARTED
FG00014 subjects
COMPLETED
FG00013 subjects
NOT COMPLETED
FG0001 subjects
Type
Comment
Reasons
Adverse Event
FG0001 subjects
All enrolled participants who received at least 1 dose of study intervention
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
All Participants
Participants underwent Period 1 to 8 and received study interventions as follows: Period 1: rosuvastatin 10mg once daily (QD) on Day 1; Period 2: midazolam 2mg QD on Day 1; Period 3: PF-06882961 (danuglipron) 10mg twice a day (BID) on Days 1-4, 20mg BID on Days 5-8, 40mg BID on Days 9-12, 60mg BID on Days 13-16, 80mg BID on Days 17-20, 100mg BID on Days 21-24, and 120mg BID on Days 25-28; Period 4: PF-06882961 120mg BID on Days 1-4 + rosuvastatin 10mg QD on Day 1; Period 5: PF-06882961 120mg BID + midazolam 2mg QD on Day 1; Period 6: PF-06882961 140mg BID on Days 1-4, 160mg BID on Days 5-8, 180mg BID on Days 9-12, and 200mg BID on Days 13-16; Period 7: PF-06882961 200mg BID on Days 1-4 + rosuvastatin 10mg QD on Day 1; Period 8: PF-06882961 200mg BID + midazolam 2mg QD on Day 1.
Denominators
Units
Counts
Participants
BG00016
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00049.0± 11.34
Age, Customized
Count of Participants
Participants
Title
Denominators
Categories
<18 Years
Title
Measurements
BG0000
18-44 Years
Title
Measurements
BG000
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0008
Male
BG0008
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
White
Title
Measurements
BG00012
Black or African American
Title
Measurements
BG000
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Area Under the Plasma Concentration-time Profile From Time 0 to Last Quantifiable Concentration (AUClast) of Rosuvastatin in Periods 1, 4 and 7
AUClast is area under the plasma concentration-time profile from time 0 to last quantifiable concentration.
The PK parameter analysis population was defined as all participants who received at least 1 dose of rosuvastatin and had at least 1 of the PK parameters of interest calculated.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram*hour per milliliter (ng*hr/mL)
At 0 (prior to rosuvastatin dose), 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 48, and 72 hours post rosuvastatin dose on Day 1 in Periods 1, 4, and 7
ID
Title
Description
OG000
Rosuvastatin 10mg (Period 1)
Participants received rosuvastatin 10mg QD on Day 1 in Period 1.
Participants received PF-06882961 200mg BID on Days 1-4 and rosuvastatin 10mg QD on Day 1 in Period 7.
Units
Counts
Participants
OG00016
OG00114
OG00214
Title
Denominators
Categories
Title
Measurements
OG00035.17± 43
OG00172.15± 50
OG002100.90± 40
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Comparison for AUClast (PF-06882961 120mg BID + rosuvastatin 10mg [Period 4] vs Rosuvastatin 10mg [Period 1])
Mixed Models Analysis
Adjusted Geometric Mean Ratio (%)
202.94
2-Sided
90
167.14
246.41
Other
The ratio and 90% confidence interval were expressed as percentages.
OG000
Primary
AUClast of Midazolam in Periods 2, 5 and 8
AUClast is area under the plasma concentration-time profile from time 0 to last quantifiable concentration.
The PK parameter analysis population was defined as all participants who received at least 1 dose of rosuvastatin and had at least 1 of the PK parameters of interest calculated.
Posted
Geometric Mean
Geometric Coefficient of Variation
nanogram*hour per milliliter (ng*hr/mL)
At 0 (prior to midazolam dose), 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours post midazolam dose on Day 1 in Periods 2, 5, and 8
ID
Title
Description
OG000
Midazolam 2mg (Period 2)
Participants received midazolam 2mg QD on Day 1 in Period 2.
OG001
PF-06882961 120mg BID + Midazolam 2mg (Period 5)
Participants received PF-06882961 120mg BID and midazolam 2mg QD on Day 1 in Period 5.
OG002
PF-06882961 200mg BID + Midazolam 2mg (Period 8)
Participants received PF-06882961 200mg BID and midazolam 2mg QD on Day 1 in Period 8.
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. A serious adverse event (SAE) was defined as any untoward medical occurrence that, at any dose: resulted in death; was life-threatening; required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity; was a congenital anomaly/birth defect; or other serious situations such as important medical events. TEAEs were events between first dose of study drug and up to follow-up visit that were absent before treatment or that worsened after treatment. AEs presented below were TEAEs. The investigator was required to use clinical judgment to assess the potential relationship between investigational product and each AE, to define an treatment-related AE.
The safety analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention.
Posted
Count of Participants
Participants
From first dose of study drug (Day 1) to telephone Follow Up (Days 89-96) (approximately up to 96 days)
ID
Title
Description
OG000
Rosuvastatin 10mg (Period 1)
Participants received rosuvastatin 10mg QD on Day 1 in Period 1.
OG001
Midazolam 2mg (Period 2)
Participants received midazolam 2mg QD on Day 1 in Period 2.
Secondary
Number of Participants With Laboratory Abnormalities (Without Regard to Baseline [BL] Abnormality)
Safety laboratory assessments included clinical chemistry, hematology, urinalysis, and other tests. Abnormality was determined at the investigator's discretion.
The analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Participants with evaluable laboratory values were analyzed.
Posted
Count of Participants
Participants
From BL (Day 1, the last pre-dose measurement in Period 1) to Follow Up visit (Days 68-71) (approximately up to 71 days)
ID
Title
Description
OG000
Rosuvastatin 10mg (Period 1)
Participants received rosuvastatin 10mg QD on Day 1 in Period 1.
OG001
Midazolam 2mg (Period 2)
Participants received midazolam 2mg QD on Day 1 in Period 2.
OG002
PF-06882961 Titration up to 120mg BID (Period 3)
Participants received PF-06882961 10mg twice a day (BID) on Days 1-4, 20mg BID on Days 5-8, 40mg BID on Days 9-12, 60mg BID on Days 13-16, 80mg BID on Days 17-20, 100mg BID on Days 21-24, and 120mg BID on Days 25-28 in Period 3.
Secondary
Number of Participants With Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria
Single, supine vital signs assessments included systolic blood pressure (BP), diastolic BP and pulse rate. Abnormality in vital signs included: pulse rate <40 beats per minute (bpm) or >120bpm; supine diastolic BP <50 millimeter of mercury (mmHg), increase and decrease in change from BL of >=20mmHg; supine systolic blood pressure <90mmHg, increase and decrease in change from BL of >=30mmHg.
The analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Participants with evaluable vital signs data were analyzed.
Posted
Count of Participants
Participants
From BL (Day 1, the last pre-dose measurement in Period 1) to Follow Up visit (Days 68-71) (approximately up to 71 days)
ID
Title
Description
OG000
Rosuvastatin 10mg (Period 1)
Participants received rosuvastatin 10mg QD on Day 1 in Period 1.
OG001
Midazolam 2mg (Period 2)
Participants received midazolam 2mg QD on Day 1 in Period 2.
OG002
PF-06882961 Titration up to 120mg BID (Period 3)
Participants received PF-06882961 10mg twice a day (BID) on Days 1-4, 20mg BID on Days 5-8, 40mg BID on Days 9-12, 60mg BID on Days 13-16, 80mg BID on Days 17-20, 100mg BID on Days 21-24, and 120mg BID on Days 25-28 in Period 3.
Secondary
Change From Baseline in Body Weight
Changes from Baseline in body weight of the participants were measured.
The analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Participants with evaluable body weight data were analyzed.
Posted
Mean
Standard Deviation
kilogram (kg)
At BL (Period 1 Day 1), on Period 3 Days 1, 8, 15 and 22, Period 4 Day 1, Period 6 Days 1 and 9, Period 7 Day 1, Period 8 Day 2, and at Follow Up visit (Days 68-71)
ID
Title
Description
OG000
All Participants
Participants underwent Period 1 to 8 and received study interventions as follows: Period 1: rosuvastatin 10mg once daily (QD) on Day 1; Period 2: midazolam 2mg QD on Day 1; Period 3: PF-06882961 (danuglipron) 10mg twice a day (BID) on Days 1-4, 20mg BID on Days 5-8, 40mg BID on Days 9-12, 60mg BID on Days 13-16, 80mg BID on Days 17-20, 100mg BID on Days 21-24, and 120mg BID on Days 25-28; Period 4: PF-06882961 120mg BID on Days 1-4 + rosuvastatin 10mg QD on Day 1; Period 5: PF-06882961 120mg BID + midazolam 2mg QD on Day 1; Period 6: PF-06882961 140mg BID on Days 1-4, 160mg BID on Days 5-8, 180mg BID on Days 9-12, and 200mg BID on Days 13-16; Period 7: PF-06882961 200mg BID on Days 1-4 + rosuvastatin 10mg QD on Day 1; Period 8: PF-06882961 200mg BID + midazolam 2mg QD on Day 1.
Units
Counts
Participants
Secondary
Number of Participants With Electrocardiogram (ECG) Data Meeting the Pre-defined Categorical Summarization Criteria
ECG assessments included pulse rate (PR), QT, QTcF intervals and QRS complex. ECG abnormalities criteria included: PR interval value >= 300msec, or BL >200msec and >=25% increase from BL, or BL <=200msec and >=50% increase from BL; QRS interval value >= 140msec, or percent change from BL >=50%; QTcF value >400 and <=480msec, or >480 and <=500 msec, or >500msec, or change from BL>30 and <=60msec, or change from BL >60msec.
The analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Participants with evaluable ECG data were analyzed.
Posted
Count of Participants
Participants
No
From BL (Day 1, the last pre-dose measurement in Period 1) to Follow Up visit (Days 68-71) (approximately up to 71 days)
ID
Title
Description
OG000
Rosuvastatin 10mg (Period 1)
Participants received rosuvastatin 10mg QD on Day 1 in Period 1.
OG001
Midazolam 2mg (Period 2)
Participants received midazolam 2mg QD on Day 1 in Period 2.
OG002
PF-06882961 Titration up to 120mg BID (Period 3)
Participants received PF-06882961 10mg twice a day (BID) on Days 1-4, 20mg BID on Days 5-8, 40mg BID on Days 9-12, 60mg BID on Days 13-16, 80mg BID on Days 17-20, 100mg BID on Days 21-24, and 120mg BID on Days 25-28 in Period 3.
Secondary
Number of Participants With Positive Response on the Columbia Suicide Severity Rating Scale (C-SSRS)
The C-SSRS was an interview-based rating scale to systematically assess suicidal ideation and suicidal behavior. C-SSRS assessed whether participant experienced any of the following 1: completed suicide, 2: suicide attempt (response of "yes" on "actual attempt"), 3: preparatory acts towards imminent suicidal behavior ("yes" on "aborted attempt", "interrupted attempt", "preparatory acts/behavior"), 4: suicidal ideation ("yes" on "wish to be dead", "non-specific active suicidal thoughts"), 7: self-injurious behavior, no suicidal intent ("yes" on "has participant engaged in non-suicidal self-injurious behavior"). In this outcome, number of participants with positive response (response of "yes") to suicidal behavior, ideation, or any self-injurious behavior were reported.
The analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Participants with evaluable C-SSRS results were analyzed.
Posted
Count of Participants
Participants
At BL (Period 1 Day 1), on Period 3 Days 1, 8, 15, and 22, Period 4 Day 1, Period 6 Days 1, 9, and 16, Period 8 Day 2, at Follow Up visit (Days 68-71) and Early Termination
ID
Title
Description
OG000
All Participants
Participants underwent Period 1 to 8 and received study interventions as follows: Period 1: rosuvastatin 10mg once daily (QD) on Day 1; Period 2: midazolam 2mg QD on Day 1; Period 3: PF-06882961 (danuglipron) 10mg twice a day (BID) on Days 1-4, 20mg BID on Days 5-8, 40mg BID on Days 9-12, 60mg BID on Days 13-16, 80mg BID on Days 17-20, 100mg BID on Days 21-24, and 120mg BID on Days 25-28; Period 4: PF-06882961 120mg BID on Days 1-4 + rosuvastatin 10mg QD on Day 1; Period 5: PF-06882961 120mg BID + midazolam 2mg QD on Day 1; Period 6: PF-06882961 140mg BID on Days 1-4, 160mg BID on Days 5-8, 180mg BID on Days 9-12, and 200mg BID on Days 13-16; Period 7: PF-06882961 200mg BID on Days 1-4 + rosuvastatin 10mg QD on Day 1; Period 8: PF-06882961 200mg BID + midazolam 2mg QD on Day 1.
Secondary
Number of Participants With Categorical Scores on the Patient Health Questionnaire (PHQ-9)
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", "several days", "more than half the days" to "nearly every day". Total score range: 0-27 (each item with scale from 0 [not at all] to 3 [nearly every day]. Higher score=greater severity).
The analysis set included all participants assigned to study intervention and who took at least 1 dose of study intervention. Participants with evaluable PHQ-9 results were analyzed.
Posted
Count of Participants
Participants
At BL (Period 1 Day 1), on Period 3 Days 1, 8, 15, and 22, Period 4 Day 1, Period 6 Days 1, 9, and 16, Period 8 Day 2, at Follow Up visit (Days 68-71) and Early Termination
ID
Title
Description
OG000
All Participants
Participants underwent Period 1 to 8 and received study interventions as follows: Period 1: rosuvastatin 10mg once daily (QD) on Day 1; Period 2: midazolam 2mg QD on Day 1; Period 3: PF-06882961 (danuglipron) 10mg twice a day (BID) on Days 1-4, 20mg BID on Days 5-8, 40mg BID on Days 9-12, 60mg BID on Days 13-16, 80mg BID on Days 17-20, 100mg BID on Days 21-24, and 120mg BID on Days 25-28; Period 4: PF-06882961 120mg BID on Days 1-4 + rosuvastatin 10mg QD on Day 1; Period 5: PF-06882961 120mg BID + midazolam 2mg QD on Day 1; Period 6: PF-06882961 140mg BID on Days 1-4, 160mg BID on Days 5-8, 180mg BID on Days 9-12, and 200mg BID on Days 13-16; Period 7: PF-06882961 200mg BID on Days 1-4 + rosuvastatin 10mg QD on Day 1; Period 8: PF-06882961 200mg BID + midazolam 2mg QD on Day 1.
Time Frame
From first dose of study drug (Day 1) to telephone Follow Up (Days 89-96) (approximately up to 96 days)
Description
SAEs and non-serious AEs were recorded on the CRF. SAEs were also reported on the Clinical Trial SAE report form to Pfizer Safety within 24 hours of awareness. The same event may appear as both an AE and an SAE. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and nonserious event during the study. Total number at risk below refers to the number of participants evaluable for SAEs or AEs.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Rosuvastatin 10mg (Period 1)
Participants received rosuvastatin 10mg QD on Day 1 in Period 1.
0
16
0
16
0
16
EG001
Midazolam 2mg (Period 2)
Participants received midazolam 2mg QD on Day 1 in Period 2.
0
16
0
16
2
16
EG002
PF-06882961 Titration up to 120mg BID (Period 3)
Participants received PF-06882961 10mg twice a day (BID) on Days 1-4, 20mg BID on Days 5-8, 40mg BID on Days 9-12, 60mg BID on Days 13-16, 80mg BID on Days 17-20, 100mg BID on Days 21-24, and 120mg BID on Days 25-28 in Period 3.
Participants received PF-06882961 200mg BID on Days 1-4 and rosuvastatin 10mg QD on Day 1 in Period 7.
0
14
0
14
7
14
EG007
PF-06882961 200mg BID + Midazolam 2mg (Period 8)
Participants received PF-06882961 200mg BID and midazolam 2mg QD on Day 1 in Period 8.
0
14
1
14
8
14
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Transaminases increased
Investigations
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG0030 affected14 at risk
EG0040 affected14 at risk
EG0050 affected14 at risk
EG0060 affected14 at risk
EG0071 affected14 at risk
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Nausea
Gastrointestinal disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0028 affected16 at risk
EG0035 affected14 at risk
EG0040 affected14 at risk
EG0054 affected14 at risk
EG0061 affected14 at risk
EG0070 affected14 at risk
Constipation
Gastrointestinal disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG00210 affected16 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0024 affected16 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0023 affected16 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0021 affected16 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0023 affected16 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0021 affected16 at risk
EG003
Retching
Gastrointestinal disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Glomerular filtration rate decreased
Investigations
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0021 affected16 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Headache
Nervous system disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0026 affected16 at risk
EG003
Dizziness
Nervous system disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0021 affected16 at risk
EG003
Somnolence
Nervous system disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0012 affected16 at risk
EG0020 affected16 at risk
EG003
Early satiety
General disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0025 affected16 at risk
EG003
Fatigue
General disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Exercise tolerance decreased
General disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Malaise
General disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0021 affected16 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Pain
General disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0021 affected16 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0022 affected16 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0022 affected16 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Muscle discomfort
Musculoskeletal and connective tissue disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0021 affected16 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Vulvovaginal mycotic infection
Infections and infestations
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Cold sweat
Skin and subcutaneous tissue disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Skin lesion
Skin and subcutaneous tissue disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Palpitations
Cardiac disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Hyperbilirubinaemia
Hepatobiliary disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0021 affected16 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA v24.0
Non-systematic Assessment
EG0000 affected16 at risk
EG0010 affected16 at risk
EG0020 affected16 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Comparison for AUClast (PF-06882961 200mg BID + rosuvastatin 10mg [Period 7] vs Rosuvastatin 10mg [Period 1])
Mixed Models Analysis
Adjusted Geometric Mean Ratio (%)
283.73
2-Sided
90
233.68
344.51
Other
The ratio and 90% confidence interval were expressed as percentages.
Units
Counts
Participants
OG00016
OG00114
OG00213
Title
Denominators
Categories
Title
Measurements
OG00039.24± 27
OG00119.98± 49
OG00220.21± 48
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Comparison for AUClast (PF-06882961 120mg BID + midazolam 2mg [Period 5] vs Midazolam 2mg [Period 2])
Mixed Models Analysis
Adjusted Geometric Mean Ratio (%)
50.57
2-Sided
90
42.27
60.50
Other
The ratio and 90% confidence interval were expressed as percentages.
OG000
OG002
Comparison for AUClast (PF-06882961 200mg BID + midazolam 2mg [Period 8] vs Midazolam 2mg [Period 2])
Mixed Models Analysis
Adjusted Geometric Mean Ratio (%)
50.56
2-Sided
90
42.06
60.78
Other
The ratio and 90% confidence interval were expressed as percentages.
OG002
PF-06882961 Titration up to 120mg BID (Period 3)
Participants received PF-06882961 10mg twice a day (BID) on Days 1-4, 20mg BID on Days 5-8, 40mg BID on Days 9-12, 60mg BID on Days 13-16, 80mg BID on Days 17-20, 100mg BID on Days 21-24, and 120mg BID on Days 25-28 in Period 3.