Trial Outcomes & Findings for A Drug-Drug Interaction Study to Examine the Impact of Itraconazole and Cyclosporine on PF-07081532 Pharmacokinetics in Overweight or Obese Adults (NCT NCT05745701)
NCT ID: NCT05745701
Last Updated: 2024-09-23
Results Overview
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.
COMPLETED
PHASE1
16 participants
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.
2024-09-23
Participant Flow
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.
Participant milestones
| Measure |
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.
|
|---|---|
|
Period 1: PF-07081532
STARTED
|
16
|
|
Period 1: PF-07081532
COMPLETED
|
16
|
|
Period 1: PF-07081532
NOT COMPLETED
|
0
|
|
Period 2: Cyclosporine + PF-07081532
STARTED
|
16
|
|
Period 2: Cyclosporine + PF-07081532
COMPLETED
|
16
|
|
Period 2: Cyclosporine + PF-07081532
NOT COMPLETED
|
0
|
|
Period 3: Itraconazole + PF-07081532
STARTED
|
16
|
|
Period 3: Itraconazole + PF-07081532
COMPLETED
|
16
|
|
Period 3: Itraconazole + PF-07081532
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
A Drug-Drug Interaction Study to Examine the Impact of Itraconazole and Cyclosporine on PF-07081532 Pharmacokinetics in Overweight or Obese Adults
Baseline characteristics by cohort
| Measure |
Lotiglipron Then Lotiglipron + Cyclosporine Then Lotiglipron + Itraconazole
n=16 Participants
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.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
16 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
36.2 Years
STANDARD_DEVIATION 11.54 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
7 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
28.6 kg/m^2
n=5 Participants
|
PRIMARY outcome
Timeframe: 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.Population: 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.
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.
Outcome measures
| Measure |
Active Comparator: Period 1: Lotiglipron
n=16 Participants
Participants received 40 mg SD lotiglipron orally on Day 1 of Period 1.
|
Experimental: Period 2: Lotiglipron + Cyclosporine
n=16 Participants
Participants received 40 mg SD lotiglipron orally and 600 mg SD cyclosporine orally on Day 1 of Period 2.
|
Experimental: Period 3: Itraconazole+Lotiglipron
n=16 Participants
Participants received 200 mg SD itraconazole orally for 9 days plus 40 mg SD lotiglipron orally on Day 4 of Period 3.
|
|---|---|---|---|
|
Area Under the Curve From Time Zero to Extrapolated Infinite Time (AUCinf) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine
|
81800 nanogram*hour/milliliter (ng*hr/mL)
Geometric Coefficient of Variation 49
|
162800 nanogram*hour/milliliter (ng*hr/mL)
Geometric Coefficient of Variation 62
|
212900 nanogram*hour/milliliter (ng*hr/mL)
Geometric Coefficient of Variation 36
|
SECONDARY outcome
Timeframe: 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 DaysPopulation: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
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.
Outcome measures
| Measure |
Active Comparator: Period 1: Lotiglipron
n=16 Participants
Participants received 40 mg SD lotiglipron orally on Day 1 of Period 1.
|
Experimental: Period 2: Lotiglipron + Cyclosporine
Participants received 40 mg SD lotiglipron orally and 600 mg SD cyclosporine orally on Day 1 of Period 2.
|
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.
|
|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
All causality TEAEs
|
11 Participants
|
—
|
—
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Treatment-Related TEAEs
|
11 Participants
|
—
|
—
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
All causality Treatment-emergent SAEs
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (pre-dose on Day 1), Period 2 Day 5 (Study Day 10), and Period 3 Day 10 (Study Day 20)Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
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.
Outcome measures
| Measure |
Active Comparator: Period 1: Lotiglipron
n=16 Participants
Participants received 40 mg SD lotiglipron orally on Day 1 of Period 1.
|
Experimental: Period 2: Lotiglipron + Cyclosporine
Participants received 40 mg SD lotiglipron orally and 600 mg SD cyclosporine orally on Day 1 of Period 2.
|
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.
|
|---|---|---|---|
|
Number of Participants With Laboratory Abnormalities
HEMATOLOGY- Ery. Mean Corpuscular Volume (fL) < 0.9*LLN
|
1 Participants
|
—
|
—
|
|
Number of Participants With Laboratory Abnormalities
HEMATOLOGY-Ery. Mean Corpuscular Hemoglobin (pg/cell) < 0.9*LLN
|
1 Participants
|
—
|
—
|
|
Number of Participants With Laboratory Abnormalities
HEMATOLOGY-Eosinophils/Leukocytes (%)> 1.2*ULN
|
1 Participants
|
—
|
—
|
|
Number of Participants With Laboratory Abnormalities
CLINICAL CHEMISTRY-Urate (mg/dL)> 1.2*ULN
|
1 Participants
|
—
|
—
|
|
Number of Participants With Laboratory Abnormalities
URINALYSIS-URINE Hemoglobin (Scalar)≥ 1
|
1 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 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)Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
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
Outcome measures
| Measure |
Active Comparator: Period 1: Lotiglipron
n=16 Participants
Participants received 40 mg SD lotiglipron orally on Day 1 of Period 1.
|
Experimental: Period 2: Lotiglipron + Cyclosporine
Participants received 40 mg SD lotiglipron orally and 600 mg SD cyclosporine orally on Day 1 of Period 2.
|
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.
|
|---|---|---|---|
|
Number of Participants Meeting Pre-Specified Criteria of Vital Signs
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 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)Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
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.
Outcome measures
| Measure |
Active Comparator: Period 1: Lotiglipron
n=16 Participants
Participants received 40 mg SD lotiglipron orally on Day 1 of Period 1.
|
Experimental: Period 2: Lotiglipron + Cyclosporine
Participants received 40 mg SD lotiglipron orally and 600 mg SD cyclosporine orally on Day 1 of Period 2.
|
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.
|
|---|---|---|---|
|
Change From Baseline in Body Weight at the End of Periods 1, 2, and 3
Baseline
|
87.631 Kilogram (kg)
Standard Deviation 12.9350
|
—
|
—
|
|
Change From Baseline in Body Weight at the End of Periods 1, 2, and 3
Day 5 of Period 1
|
-1.631 Kilogram (kg)
Standard Deviation 1.1904
|
—
|
—
|
|
Change From Baseline in Body Weight at the End of Periods 1, 2, and 3
Day 5 of Period 2
|
-1.956 Kilogram (kg)
Standard Deviation 1.4778
|
—
|
—
|
|
Change From Baseline in Body Weight at the End of Periods 1, 2, and 3
Day 10 of Period 3
|
-2.256 Kilogram (kg)
Standard Deviation 1.6541
|
—
|
—
|
SECONDARY outcome
Timeframe: 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)Population: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
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.
Outcome measures
| Measure |
Active Comparator: Period 1: Lotiglipron
n=16 Participants
Participants received 40 mg SD lotiglipron orally on Day 1 of Period 1.
|
Experimental: Period 2: Lotiglipron + Cyclosporine
Participants received 40 mg SD lotiglipron orally and 600 mg SD cyclosporine orally on Day 1 of Period 2.
|
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.
|
|---|---|---|---|
|
Number of Participants Meeting Pre-Specified Criteria of Electrocardiogram (ECGs)
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Period 1 Day -1 (Study Day -1), Period 3 Day 10 (Study Day 20) or Early Termination visitPopulation: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
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.
Outcome measures
| Measure |
Active Comparator: Period 1: Lotiglipron
n=16 Participants
Participants received 40 mg SD lotiglipron orally on Day 1 of Period 1.
|
Experimental: Period 2: Lotiglipron + Cyclosporine
Participants received 40 mg SD lotiglipron orally and 600 mg SD cyclosporine orally on Day 1 of Period 2.
|
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.
|
|---|---|---|---|
|
Number of Participants With Suicidal Ideation or Behavior According to Columbia Suicide Severity Rating Scale (C-SSRS)
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: Period 1 Day -1 (Study Day -1), Period 3 Day 10 (Study Day 20) or Early Termination visitPopulation: All participants randomly assigned to study intervention and who took at least 1 dose of study intervention.
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
Outcome measures
| Measure |
Active Comparator: Period 1: Lotiglipron
n=16 Participants
Participants received 40 mg SD lotiglipron orally on Day 1 of Period 1.
|
Experimental: Period 2: Lotiglipron + Cyclosporine
Participants received 40 mg SD lotiglipron orally and 600 mg SD cyclosporine orally on Day 1 of Period 2.
|
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.
|
|---|---|---|---|
|
Number of Participants With a Score of ≥15 on Patient Health Questionnaire-9 (PHQ-9)
|
0 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 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.Population: 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.
Cmax is the maximum observed concentration and is observed directly from data.
Outcome measures
| Measure |
Active Comparator: Period 1: Lotiglipron
n=16 Participants
Participants received 40 mg SD lotiglipron orally on Day 1 of Period 1.
|
Experimental: Period 2: Lotiglipron + Cyclosporine
n=16 Participants
Participants received 40 mg SD lotiglipron orally and 600 mg SD cyclosporine orally on Day 1 of Period 2.
|
Experimental: Period 3: Itraconazole+Lotiglipron
n=16 Participants
Participants received 200 mg SD itraconazole orally for 9 days plus 40 mg SD lotiglipron orally on Day 4 of Period 3.
|
|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine
|
4165 nanogram/milliliter (ng/mL)
Geometric Coefficient of Variation 28
|
5207 nanogram/milliliter (ng/mL)
Geometric Coefficient of Variation 35
|
5180 nanogram/milliliter (ng/mL)
Geometric Coefficient of Variation 24
|
SECONDARY outcome
Timeframe: 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.Population: 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.
Tmax is the Time to Cmax and is observed directly from data as time of first occurrence.
Outcome measures
| Measure |
Active Comparator: Period 1: Lotiglipron
n=16 Participants
Participants received 40 mg SD lotiglipron orally on Day 1 of Period 1.
|
Experimental: Period 2: Lotiglipron + Cyclosporine
n=16 Participants
Participants received 40 mg SD lotiglipron orally and 600 mg SD cyclosporine orally on Day 1 of Period 2.
|
Experimental: Period 3: Itraconazole+Lotiglipron
n=16 Participants
Participants received 200 mg SD itraconazole orally for 9 days plus 40 mg SD lotiglipron orally on Day 4 of Period 3.
|
|---|---|---|---|
|
Time to Cmax (Tmax) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine
|
6.00 hr
Interval 3.98 to 8.0
|
6.00 hr
Interval 2.0 to 12.0
|
5.03 hr
Interval 2.0 to 10.0
|
SECONDARY outcome
Timeframe: 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.Population: 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.
CL/F is the apparent oral clearance and is calculated by Dose/AUCinf.
Outcome measures
| Measure |
Active Comparator: Period 1: Lotiglipron
n=16 Participants
Participants received 40 mg SD lotiglipron orally on Day 1 of Period 1.
|
Experimental: Period 2: Lotiglipron + Cyclosporine
n=16 Participants
Participants received 40 mg SD lotiglipron orally and 600 mg SD cyclosporine orally on Day 1 of Period 2.
|
Experimental: Period 3: Itraconazole+Lotiglipron
n=16 Participants
Participants received 200 mg SD itraconazole orally for 9 days plus 40 mg SD lotiglipron orally on Day 4 of Period 3.
|
|---|---|---|---|
|
Apparent Oral Clearance (CL/F) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine
|
0.4890 Litre (L)/hr
Geometric Coefficient of Variation 49
|
0.2458 Litre (L)/hr
Geometric Coefficient of Variation 62
|
0.1879 Litre (L)/hr
Geometric Coefficient of Variation 36
|
SECONDARY outcome
Timeframe: 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.Population: 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.
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
Outcome measures
| Measure |
Active Comparator: Period 1: Lotiglipron
n=16 Participants
Participants received 40 mg SD lotiglipron orally on Day 1 of Period 1.
|
Experimental: Period 2: Lotiglipron + Cyclosporine
n=16 Participants
Participants received 40 mg SD lotiglipron orally and 600 mg SD cyclosporine orally on Day 1 of Period 2.
|
Experimental: Period 3: Itraconazole+Lotiglipron
n=16 Participants
Participants received 200 mg SD itraconazole orally for 9 days plus 40 mg SD lotiglipron orally on Day 4 of Period 3.
|
|---|---|---|---|
|
Apparent Oral Volume of Distribution (Vz/F) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine
|
15.01 Litre
Geometric Coefficient of Variation 31
|
8.261 Litre
Geometric Coefficient of Variation 47
|
11.91 Litre
Geometric Coefficient of Variation 28
|
SECONDARY outcome
Timeframe: 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.Population: 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.
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.
Outcome measures
| Measure |
Active Comparator: Period 1: Lotiglipron
n=16 Participants
Participants received 40 mg SD lotiglipron orally on Day 1 of Period 1.
|
Experimental: Period 2: Lotiglipron + Cyclosporine
n=16 Participants
Participants received 40 mg SD lotiglipron orally and 600 mg SD cyclosporine orally on Day 1 of Period 2.
|
Experimental: Period 3: Itraconazole+Lotiglipron
n=16 Participants
Participants received 200 mg SD itraconazole orally for 9 days plus 40 mg SD lotiglipron orally on Day 4 of Period 3.
|
|---|---|---|---|
|
Terminal Half-life (t1/2) of Lotiglipron When Administered Alone and With Itraconazole or Cyclosporine
|
21.96 hr
Standard Deviation 6.1239
|
24.14 hr
Standard Deviation 7.3865
|
45.02 hr
Standard Deviation 9.7607
|
Adverse Events
Lotiglipron Then Lotiglipron + Cyclosporine Then Lotiglipron + Itraconazole
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Lotiglipron Then Lotiglipron + Cyclosporine Then Lotiglipron + Itraconazole
n=16 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Abdominal discomfort
|
6.2%
1/16 • 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
|
|
Gastrointestinal disorders
Abdominal distension
|
6.2%
1/16 • 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
|
|
Gastrointestinal disorders
Abdominal pain
|
12.5%
2/16 • 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
|
|
Gastrointestinal disorders
Constipation
|
12.5%
2/16 • 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
|
|
Gastrointestinal disorders
Diarrhoea
|
18.8%
3/16 • 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
|
|
Gastrointestinal disorders
Dyspepsia
|
25.0%
4/16 • 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
|
|
Gastrointestinal disorders
Eructation
|
6.2%
1/16 • 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
|
|
Gastrointestinal disorders
Nausea
|
43.8%
7/16 • 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
|
|
Gastrointestinal disorders
Vomiting
|
12.5%
2/16 • 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
|
|
General disorders
Fatigue
|
12.5%
2/16 • 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
|
|
General disorders
Feeling hot
|
37.5%
6/16 • 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
|
|
Injury, poisoning and procedural complications
Scratch
|
6.2%
1/16 • 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
|
|
Metabolism and nutrition disorders
Decreased appetite
|
25.0%
4/16 • 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
|
|
Nervous system disorders
Dizziness
|
6.2%
1/16 • 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
|
|
Nervous system disorders
Dizziness postural
|
6.2%
1/16 • 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
|
|
Nervous system disorders
Headache
|
25.0%
4/16 • 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
|
|
Nervous system disorders
Hypoaesthesia
|
6.2%
1/16 • 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
|
|
Nervous system disorders
Somnolence
|
6.2%
1/16 • 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
|
|
Psychiatric disorders
Somatic symptom disorder
|
6.2%
1/16 • 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
|
|
Renal and urinary disorders
Chromaturia
|
6.2%
1/16 • 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
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
12.5%
2/16 • 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
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
6.2%
1/16 • 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
|
|
Vascular disorders
Hot flush
|
6.2%
1/16 • 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
|
|
Vascular disorders
Phlebitis
|
12.5%
2/16 • 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
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place