Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
This is a Phase 1, open-label, fixed-sequence, 3-period study to evaluate the effect of multiple doses of itraconazole and a single dose of cyclosporine on the single-dose PK of PF-07081532 in otherwise healthy, overweight or obese, adult female and male participants.
The 3 study periods will be conducted consecutively without a break.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Period 1: PF-07081532 | Active Comparator | Participants will receive PF-07081532 as a single dose on Day 1. |
|
| Period 2: Cyclosporine + PF-07081532 | Experimental | Participants will receive a single dose of PF-07081532 and a single dose of cyclosporine on Day 1. |
|
| Period 3: Itraconazole + PF-07081532 | Experimental | Participants will receive itraconazole daily for 9 days plus a single dose of PF-07081532 on Day 4. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| PF-07081532 | Drug | Oral Tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine | AUCinf is area under the plasma concentration-time profile from time zero extrapolated to infinite time. AUCinf is caluculated by AUClast + (Clast/kel), where Clast is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis. | Pre-dose of lotiglipron and at 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, and 144 (for Period 3 only) hours post dose of lotiglipron on Day 1 of Periods 1 and 2 and on Day 4 of Period 3. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a 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 an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. Any AEs occurring following start of treatment were considered as treatment emergent adverse event (TEAE). Events that occur during follow-up within the lag time of up to 35 days after the last dose of study intervention were counted as treatment emergent and attributed to the last treatment taken. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| New Haven Clinical Research Unit | New Haven | Connecticut | 06511 | United States |
Not provided
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
Not provided
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.
Not provided
Not provided
Not provided
Not provided
A total of 16 participants were enrolled in the study. All enrolled participants received 3-period treatments in a fixed sequence. All enrolled participants were treated and completed the study.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Lotiglipron (PF-07081532) Then Lotiglipron + Cyclosporine Then Lotiglipron + Itraconazole | Period 1 (Study Days -1 to 5): Participants received 40 milligram (mg) single dose (SD) lotiglipron orally on Day 1 of Period 1. Period 1 was followed by Period 2. Period 2 (Study Days 6 to 10): Participants received 40 mg SD lotiglipron orally and a 600 mg SD cyclosporine orally on Day 1 of Period 2. Period 2 was followed by Period 3. Period 3 (Study Days 11 to 20): Participants received 200 mg SD itraconazole orally for 9 days and 40 mg SD lotiglipron orally on Day 4 of Period 3. Participants were followed up to maximum of 35 days from the last dose of study intervention. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Period 1: PF-07081532 |
| |||||||||||||
| Period 2: Cyclosporine + PF-07081532 |
| |||||||||||||
| Period 3: Itraconazole + PF-07081532 |
|
This group includes all participants who enrolled in this study and received at least 1 dose of study intervention.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Lotiglipron Then Lotiglipron + Cyclosporine Then Lotiglipron + Itraconazole | Period 1 (Study Days -1 to 5): Participants received 40 mg SD lotiglipron orally on Day 1 of Period 1. Period 1 was followed by Period 2. Period 2 (Study Days 6 to 10): Participants received 40 mg SD lotiglipron orally and a 600 mg SD cyclosporine orally on Day 1 of Period 2. Period 2 was followed by Period 3. Period 3 (Study Days 11 to 20): Participants received 200 mg SD itraconazole orally for 9 days and 40 mg SD lotiglipron orally on Day 4 of Period 3. Participants were followed up to maximum of 35 days from the last dose of study intervention. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| 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 Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine | AUCinf is area under the plasma concentration-time profile from time zero extrapolated to infinite time. AUCinf is caluculated by AUClast + (Clast/kel), where Clast is the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis. | All participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported. The outcome measure was reported by 3 arms to characterize the effect of MD itraconazole and SD cyclosporine on the single dose PK of lotiglipron. The 120-hour PK samples collected in Period 1 was the same as the pre-dose PK samples in Periods 2. The 120-hour PK sample from Period 2 was taken on Day 1 of Period 3 prior to itraconazole dose administration. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour/milliliter (ng*hr/mL) | Pre-dose of lotiglipron and at 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, and 144 (for Period 3 only) hours post dose of lotiglipron on Day 1 of Periods 1 and 2 and on Day 4 of Period 3. |
From the first dose up to 35 days after administration of the final dose of study intervention (Period 3 Day 9, Study Day 19), the maximum duration was 54 Days
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lotiglipron Then Lotiglipron + Cyclosporine Then Lotiglipron + Itraconazole | Period 1 (Study Days -1 to 5): Participants received 40 mg SD lotiglipron orally on Day 1 of Period 1. Period 1 was followed by Period 2. Period 2 (Study Days 6 to 10): Participants received 40 mg SD lotiglipron orally and a 600 mg SD cyclosporine orally on Day 1 of Period 2. Period 2 was followed by Period 3. Period 3 (Study Days 11 to 20): Participants received 200 mg SD itraconazole orally for 9 days and 40 mg SD lotiglipron orally on Day 4 of Period 3. Participants were followed up to maximum of 35 days from the last dose of study intervention. |
Not provided
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA v26.0 | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 31, 2023 | May 21, 2024 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 22, 2023 | May 21, 2024 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D017964 | Itraconazole |
| ID | Term |
|---|---|
| D014230 | Triazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Cyclosporine | Device | Oral Solution |
|
| Itraconazole | Drug | Oral Capsule |
|
| From the first dose up to 35 days after administration of the final dose of study intervention (Period 3 Day 9, Study Day 19), the maximum duration was 54 Days |
| Number of Participants With Laboratory Abnormalities | Participants with laboratory abnormalities (without regard to baseline abnormality) that met pre-specified criteria: For HEMATOLOGY, 1) Erythrocyte (Ery.) Mean Corpuscular Volume (fL) < 0.9*Lower limit of normal (LLN), 2) Ery. Mean Corpuscular Hemoglobin (picograms [pg]/cell) < 0.9*LLN; 3） Eosinophils/Leukocytes (%)> 1.2*upper limit of normal (ULN); for CLINICAL CHEMISTRY, Urate (mg/dL)> 1.2*ULN; for URINALYSIS, Urine Hemoglobin (Scalar)≥ 1. | Baseline (pre-dose on Day 1), Period 2 Day 5 (Study Day 10), and Period 3 Day 10 (Study Day 20) |
| Number of Participants Meeting Pre-Specified Criteria of Vital Signs | Pre-specified criteria of vital signs included: Supine diastolic blood pressure (BP) <50mmHg, change from baseline maximum (max) decrease or increase >=20mmHg; supine pulse rate min< 40 beats per minute (bpm), max> 120 bpm; Supine systolic BP: Value <90 mmHg, change from baseline max decrease or increase >=30mmHg | Pre-dose Day 1 in periods 1, 2 and 3 (Study Days 1, 6, and 11, respectively), and prior to discharge on Period 3 Day 10 (Study Day 20) |
| Change From Baseline in Body Weight at the End of Periods 1, 2, and 3 | Observed value at baseline and change from baseline in body weight at Day 5 of Period 1 , Day 5 of Period 2, and Day 10 of Period 3 were summarized. | Baseline (pre-dose on Day 1), Day 5 of Period 1 (Study Day 5), Day 5 of Period 2 (Study Day 10), and Day 10 of Period 3 (Study Day 20) |
| Number of Participants Meeting Pre-Specified Criteria of Electrocardiogram (ECGs) | The pre-specified criteria of ECG included: QT interval, aggregated: value >500 millisecond (msec); corrected QT Fridericia method (QTCF) interval, aggregated: 450<=value<480 msec, 480<=value<500 msec, value>=500 msec, 30<=changes<60msec, and changes>=60msec. | Pre-dose Day 1 in periods 1, 2 and 3 (Study Days 1, 6, and 11, respectively), and prior to discharge on Period 3 Day 10 (Study Day 20) |
| Number of Participants With Suicidal Ideation or Behavior 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 question related to suicidal ideation or behavioral are reported in this outcome measure. | Period 1 Day -1 (Study Day -1), Period 3 Day 10 (Study Day 20) or Early Termination visit |
| 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 was reported in this outcome measure. The total score ranges from 0 to 27 with the following interpretation: Score 1-4: minimal depression; Score 5-9: Mild depression; Score 10-14: moderate depression; Score 15-19 moderately severe depression; Score 20-27: Severe depression | Period 1 Day -1 (Study Day -1), Period 3 Day 10 (Study Day 20) or Early Termination visit |
| Maximum Observed Plasma Concentration (Cmax) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine | Cmax is the maximum observed concentration and is observed directly from data. | Pre-dose of lotiglipron and at 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, and 144 (for Period 3 only) hours post dose of lotiglipron on Day 1 of Periods 1 and 2 and on Day 4 of Period 3. |
| Time to Cmax (Tmax) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine | Tmax is the Time to Cmax and is observed directly from data as time of first occurrence. | Pre-dose of lotiglipron and at 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, and 144 (for Period 3 only) hours post dose of lotiglipron on Day 1 of Periods 1 and 2 and on Day 4 of Period 3. |
| Apparent Oral Clearance (CL/F) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine | CL/F is the apparent oral clearance and is calculated by Dose/AUCinf. | Pre-dose of lotiglipron and at 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, and 144 (for Period 3 only) hours post dose of lotiglipron on Day 1 of Periods 1 and 2 and on Day 4 of Period 3. |
| Apparent Oral Volume of Distribution (Vz/F) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine | Vz/F is the apparent volume of distribution and is calculated by Dose/ (AUCinf*kel), where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve | Pre-dose of lotiglipron and at 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, and 144 (for Period 3 only) hours post dose of lotiglipron on Day 1 of Periods 1 and 2 and on Day 4 of Period 3. |
| Terminal Half-life (t1/2) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine | T1/2 is calculated by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression. | Pre-dose of lotiglipron and at 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, and 144 (for Period 3 only) hours post dose of lotiglipron on Day 1 of Periods 1 and 2 and on Day 4 of Period 3. |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Body Mass Index (BMI) | Body Mass Index (kg/m^2) = weight (kg) / [0.01✕height (cm)]^2 | Median | Full Range | kg/m^2 |
|
| ID | Title | Description |
|---|---|---|
| OG000 | Active Comparator: Period 1: Lotiglipron | Participants received 40 mg SD lotiglipron orally on Day 1 of Period 1. |
| OG001 | Experimental: Period 2: Lotiglipron + Cyclosporine | Participants received 40 mg SD lotiglipron orally and 600 mg SD cyclosporine orally on Day 1 of Period 2. |
| OG002 | Experimental: Period 3: Itraconazole+Lotiglipron | Participants received 200 mg SD itraconazole orally for 9 days plus 40 mg SD lotiglipron orally on Day 4 of Period 3. |
|
|
|
| Secondary | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a 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 an AE: 1. resulting in death, 2. was life-threatening, 3. required inpatient hospitalization or prolongation of existing hospitalization, 4. resulted in persistent disability, 5. was a congenital anomaly/birth defect, or considered to be an important medical event. Any AEs occurring following start of treatment were considered as treatment emergent adverse event (TEAE). Events that occur during follow-up within the lag time of up to 35 days after the last dose of study intervention were counted as treatment emergent and attributed to the last treatment taken. | All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | From the first dose up to 35 days after administration of the final dose of study intervention (Period 3 Day 9, Study Day 19), the maximum duration was 54 Days |
|
|
|
| Secondary | Number of Participants With Laboratory Abnormalities | Participants with laboratory abnormalities (without regard to baseline abnormality) that met pre-specified criteria: For HEMATOLOGY, 1) Erythrocyte (Ery.) Mean Corpuscular Volume (fL) < 0.9*Lower limit of normal (LLN), 2) Ery. Mean Corpuscular Hemoglobin (picograms [pg]/cell) < 0.9*LLN; 3） Eosinophils/Leukocytes (%)> 1.2*upper limit of normal (ULN); for CLINICAL CHEMISTRY, Urate (mg/dL)> 1.2*ULN; for URINALYSIS, Urine Hemoglobin (Scalar)≥ 1. | All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | Baseline (pre-dose on Day 1), Period 2 Day 5 (Study Day 10), and Period 3 Day 10 (Study Day 20) |
|
|
|
| Secondary | Number of Participants Meeting Pre-Specified Criteria of Vital Signs | Pre-specified criteria of vital signs included: Supine diastolic blood pressure (BP) <50mmHg, change from baseline maximum (max) decrease or increase >=20mmHg; supine pulse rate min< 40 beats per minute (bpm), max> 120 bpm; Supine systolic BP: Value <90 mmHg, change from baseline max decrease or increase >=30mmHg | All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | Pre-dose Day 1 in periods 1, 2 and 3 (Study Days 1, 6, and 11, respectively), and prior to discharge on Period 3 Day 10 (Study Day 20) |
|
|
|
| Secondary | Change From Baseline in Body Weight at the End of Periods 1, 2, and 3 | Observed value at baseline and change from baseline in body weight at Day 5 of Period 1 , Day 5 of Period 2, and Day 10 of Period 3 were summarized. | All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. | Posted | Mean | Standard Deviation | Kilogram (kg) | Baseline (pre-dose on Day 1), Day 5 of Period 1 (Study Day 5), Day 5 of Period 2 (Study Day 10), and Day 10 of Period 3 (Study Day 20) |
|
|
|
| Secondary | Number of Participants Meeting Pre-Specified Criteria of Electrocardiogram (ECGs) | The pre-specified criteria of ECG included: QT interval, aggregated: value >500 millisecond (msec); corrected QT Fridericia method (QTCF) interval, aggregated: 450<=value<480 msec, 480<=value<500 msec, value>=500 msec, 30<=changes<60msec, and changes>=60msec. | All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | Pre-dose Day 1 in periods 1, 2 and 3 (Study Days 1, 6, and 11, respectively), and prior to discharge on Period 3 Day 10 (Study Day 20) |
|
|
|
| Secondary | Number of Participants With Suicidal Ideation or Behavior 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 question related to suicidal ideation or behavioral are reported in this outcome measure. | All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | Period 1 Day -1 (Study Day -1), Period 3 Day 10 (Study Day 20) or Early Termination visit |
|
|
|
| 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 was reported in this outcome measure. The total score ranges from 0 to 27 with the following interpretation: Score 1-4: minimal depression; Score 5-9: Mild depression; Score 10-14: moderate depression; Score 15-19 moderately severe depression; Score 20-27: Severe depression | All participants randomly assigned to study intervention and who took at least 1 dose of study intervention. | Posted | Count of Participants | Participants | Period 1 Day -1 (Study Day -1), Period 3 Day 10 (Study Day 20) or Early Termination visit |
|
|
|
| Secondary | Maximum Observed Plasma Concentration (Cmax) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine | Cmax is the maximum observed concentration and is observed directly from data. | All participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported. The outcome measure was reported by 3 arms to characterize the effect of MD itraconazole and SD cyclosporine on the single dose PK of lotiglipron. The 120-hour PK samples collected in Period 1 was the same as the pre-dose PK samples in Periods 2. The 120-hour PK sample from Period 2 was taken on Day 1 of Period 3 prior to itraconazole dose administration. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram/milliliter (ng/mL) | Pre-dose of lotiglipron and at 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, and 144 (for Period 3 only) hours post dose of lotiglipron on Day 1 of Periods 1 and 2 and on Day 4 of Period 3. |
|
|
|
| Secondary | Time to Cmax (Tmax) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine | Tmax is the Time to Cmax and is observed directly from data as time of first occurrence. | All participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported. The outcome measure was reported by 3 arms to characterize the effect of MD itraconazole and SD cyclosporine on the single dose PK of lotiglipron. The 120-hour PK samples collected in Period 1 was the same as the pre-dose PK samples in Periods 2. The 120-hour PK sample from Period 2 was taken on Day 1 of Period 3 prior to itraconazole dose administration. | Posted | Median | Full Range | hr | Pre-dose of lotiglipron and at 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, and 144 (for Period 3 only) hours post dose of lotiglipron on Day 1 of Periods 1 and 2 and on Day 4 of Period 3. |
|
|
|
| Secondary | Apparent Oral Clearance (CL/F) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine | CL/F is the apparent oral clearance and is calculated by Dose/AUCinf. | All participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported. The outcome measure was reported by 3 arms to characterize the effect of MD itraconazole and SD cyclosporine on the single dose PK of lotiglipron. The 120-hour PK samples collected in Period 1 was the same as the pre-dose PK samples in Periods 2. The 120-hour PK sample from Period 2 was taken on Day 1 of Period 3 prior to itraconazole dose administration. | Posted | Geometric Mean | Geometric Coefficient of Variation | Litre (L)/hr | Pre-dose of lotiglipron and at 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, and 144 (for Period 3 only) hours post dose of lotiglipron on Day 1 of Periods 1 and 2 and on Day 4 of Period 3. |
|
|
|
| Secondary | Apparent Oral Volume of Distribution (Vz/F) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine | Vz/F is the apparent volume of distribution and is calculated by Dose/ (AUCinf*kel), where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve | All participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported. The outcome measure was reported by 3 arms to characterize the effect of MD itraconazole and SD cyclosporine on the single dose PK of lotiglipron. The 120-hour PK samples collected in Period 1 was the same as the pre-dose PK samples in Periods 2. The 120-hour PK sample from Period 2 was taken on Day 1 of Period 3 prior to itraconazole dose administration. | Posted | Geometric Mean | Geometric Coefficient of Variation | Litre | Pre-dose of lotiglipron and at 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, and 144 (for Period 3 only) hours post dose of lotiglipron on Day 1 of Periods 1 and 2 and on Day 4 of Period 3. |
|
|
|
| Secondary | Terminal Half-life (t1/2) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine | T1/2 is calculated by Loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration time curve. Only those data points judged to describe the terminal log linear decline were used in the regression. | All participants who took at least 1 dose of study intervention and in whom at least 1 of the PK parameters of primary interest were reported. The outcome measure was reported by 3 arms to characterize the effect of MD itraconazole and SD cyclosporine on the single dose PK of lotiglipron. The 120-hour PK samples collected in Period 1 was the same as the pre-dose PK samples in Periods 2. The 120-hour PK sample from Period 2 was taken on Day 1 of Period 3 prior to itraconazole dose administration. | Posted | Mean | Standard Deviation | hr | Pre-dose of lotiglipron and at 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 24, 36, 48, 72, 96, 120, and 144 (for Period 3 only) hours post dose of lotiglipron on Day 1 of Periods 1 and 2 and on Day 4 of Period 3. |
|
|
|
| 0 |
| 16 |
| 0 |
| 16 |
| 11 |
| 16 |
| Abdominal distension | Gastrointestinal disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Eructation | Gastrointestinal disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Feeling hot | General disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Scratch | Injury, poisoning and procedural complications | MedDRA v26.0 | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Dizziness postural | Nervous system disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Somnolence | Nervous system disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Somatic symptom disorder | Psychiatric disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Chromaturia | Renal and urinary disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Dysmenorrhoea | Reproductive system and breast disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA v26.0 | Non-systematic Assessment |
|
| Phlebitis | Vascular disorders | MedDRA v26.0 | Non-systematic Assessment |
|
Not provided
Not provided
Not provided
| D010879 |
| Piperazines |
| Title | Measurements |
|---|---|
|
|
| CLINICAL CHEMISTRY-Urate (mg/dL)> 1.2*ULN |
|
| URINALYSIS-URINE Hemoglobin (Scalar)≥ 1 |
|
| Title | Measurements |
|---|---|
|
| Day 10 of Period 3 |
|