Trial Outcomes & Findings for Drug-Drug Interaction Study Between TAK-272 and Itraconazole, Digoxin or Midazolam (NCT NCT02370615)
NCT ID: NCT02370615
Last Updated: 2016-05-23
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
34 participants
Primary outcome timeframe
Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + Itraconazole
Results posted on
2016-05-23
Participant Flow
Participants took part in the study at 1 investigative site in Japan from 25-February-2015 to 16-April-2015.
Healthy Japanese adult male participants were enrolled to receive TAK-272 and itraconazole in cohort 1 or TAK-272 and digoxin/midazolam in cohort 2.
Participant milestones
| Measure |
Cohort 1: TAK-272 + Itraconazole
TAK-272 40 milligram (mg), tablet, orally, once on Day 1 and 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
Cohort 2: Midazolam + Digoxin + TAK-272
Midazolam 2 mg, syrup, and Digoxin 0.25 mg, tablet, orally, once on Day 1 and 7, followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8.
|
|---|---|---|
|
Overall Study
STARTED
|
16
|
18
|
|
Overall Study
COMPLETED
|
15
|
18
|
|
Overall Study
NOT COMPLETED
|
1
|
0
|
Reasons for withdrawal
| Measure |
Cohort 1: TAK-272 + Itraconazole
TAK-272 40 milligram (mg), tablet, orally, once on Day 1 and 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
Cohort 2: Midazolam + Digoxin + TAK-272
Midazolam 2 mg, syrup, and Digoxin 0.25 mg, tablet, orally, once on Day 1 and 7, followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8.
|
|---|---|---|
|
Overall Study
Adverse Event
|
1
|
0
|
Baseline Characteristics
Drug-Drug Interaction Study Between TAK-272 and Itraconazole, Digoxin or Midazolam
Baseline characteristics by cohort
| Measure |
Cohort 1: TAK-272 + Itraconazole
n=15 Participants
TAK-272 40 milligram (mg), tablet, orally, once on Day 1 and 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
Cohort 2: Midazolam + Digoxin + TAK-272
n=18 Participants
Midazolam 2 mg, syrup, and Digoxin 0.25 mg, tablet, orally, once on Day 1 and 7, followed by TAK-272 80 mg, tablet, orally, once on Day 3 to 8.
|
Total
n=33 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
26.8 years
STANDARD_DEVIATION 4.11 • n=93 Participants
|
25.3 years
STANDARD_DEVIATION 4.44 • n=4 Participants
|
26.0 years
STANDARD_DEVIATION 4.30 • n=27 Participants
|
|
Sex/Gender, Customized
Male
|
15 participants
n=93 Participants
|
18 participants
n=4 Participants
|
33 participants
n=27 Participants
|
|
Smoking Classification
Never smoked
|
12 participants
n=93 Participants
|
12 participants
n=4 Participants
|
24 participants
n=27 Participants
|
|
Smoking Classification
Current smoker
|
1 participants
n=93 Participants
|
1 participants
n=4 Participants
|
2 participants
n=27 Participants
|
|
Smoking Classification
Ex-smoker
|
2 participants
n=93 Participants
|
5 participants
n=4 Participants
|
7 participants
n=27 Participants
|
|
Alcohol Classification
Drinks a few days per week
|
5 participants
n=93 Participants
|
2 participants
n=4 Participants
|
7 participants
n=27 Participants
|
|
Alcohol Classification
Drinks a few days per month
|
5 participants
n=93 Participants
|
5 participants
n=4 Participants
|
10 participants
n=27 Participants
|
|
Alcohol Classification
Does not drink
|
5 participants
n=93 Participants
|
11 participants
n=4 Participants
|
16 participants
n=27 Participants
|
|
Caffeine Classification
Caffeine consumption
|
7 participants
n=93 Participants
|
6 participants
n=4 Participants
|
13 participants
n=27 Participants
|
|
Caffeine Classification
No caffeine consumption
|
8 participants
n=93 Participants
|
12 participants
n=4 Participants
|
20 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + ItraconazolePopulation: The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics.
Outcome measures
| Measure |
Cohort 1: TAK-272
n=15 Participants
TAK-272 40 mg, tablet, orally, once on Day 1.
|
Cohort 1: TAK-272 + Itraconazole
n=15 Participants
TAK-272 40 mg, tablet, orally, once on Day 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
|---|---|---|
|
Cmax: Maximum Observed Plasma Concentration for TAK 272F and TAK 272-Metabolite (M-I) in Cohort 1
TAK 272
|
387.8 nanogram per milliliter (ng/mL)
Standard Deviation 286.18
|
780.3 nanogram per milliliter (ng/mL)
Standard Deviation 258.45
|
|
Cmax: Maximum Observed Plasma Concentration for TAK 272F and TAK 272-Metabolite (M-I) in Cohort 1
TAK 272-M-I
|
10.02 nanogram per milliliter (ng/mL)
Standard Deviation 7.1545
|
0.9550 nanogram per milliliter (ng/mL)
Standard Deviation 0.55302
|
PRIMARY outcome
Timeframe: Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + ItraconazolePopulation: The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics.
Outcome measures
| Measure |
Cohort 1: TAK-272
n=15 Participants
TAK-272 40 mg, tablet, orally, once on Day 1.
|
Cohort 1: TAK-272 + Itraconazole
n=15 Participants
TAK-272 40 mg, tablet, orally, once on Day 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
|---|---|---|
|
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK 272F and TAK 272-M-I in Cohort 1
TAK 272
|
1861 nanogram hours per milliliter (ng*hr/mL)
Standard Deviation 731.14
|
9098 nanogram hours per milliliter (ng*hr/mL)
Standard Deviation 2809.8
|
|
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK 272F and TAK 272-M-I in Cohort 1
TAK 272-M-I
|
46.53 nanogram hours per milliliter (ng*hr/mL)
Standard Deviation 19.347
|
9.373 nanogram hours per milliliter (ng*hr/mL)
Standard Deviation 8.9682
|
PRIMARY outcome
Timeframe: Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + ItraconazolePopulation: The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics.
Outcome measures
| Measure |
Cohort 1: TAK-272
n=15 Participants
TAK-272 40 mg, tablet, orally, once on Day 1.
|
Cohort 1: TAK-272 + Itraconazole
n=15 Participants
TAK-272 40 mg, tablet, orally, once on Day 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
|---|---|---|
|
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK 272F and TAK 272-M-I in Cohort 1
TAK 272
|
1842 ng*hr/mL
Standard Deviation 728.15
|
8659 ng*hr/mL
Standard Deviation 2596.7
|
|
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK 272F and TAK 272-M-I in Cohort 1
TAK 272-M-I
|
38.34 ng*hr/mL
Standard Deviation 16.944
|
0.9092 ng*hr/mL
Standard Deviation 1.5900
|
PRIMARY outcome
Timeframe: Day 1 and Day 10: pre-dose and at multiple time-points (upto 72 hours) postdose; Day 1 for Cohort 1: TAK-272 and Day 10 for Cohort 1: TAK-272 + ItraconazolePopulation: The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics.
Outcome measures
| Measure |
Cohort 1: TAK-272
n=15 Participants
TAK-272 40 mg, tablet, orally, once on Day 1.
|
Cohort 1: TAK-272 + Itraconazole
n=15 Participants
TAK-272 40 mg, tablet, orally, once on Day 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
|---|---|---|
|
Cumulative Urinary Excretion Ratio of TAK 272F and TAK 272-M-I From 0 to 72 Hours Postdose in Cohort 1
TAK 272
|
11.523 percentage of dose
Standard Deviation 2.6615
|
37.803 percentage of dose
Standard Deviation 5.4878
|
|
Cumulative Urinary Excretion Ratio of TAK 272F and TAK 272-M-I From 0 to 72 Hours Postdose in Cohort 1
TAK 272-M-I
|
0.556 percentage of dose
Standard Deviation 0.1534
|
0.071 percentage of dose
Standard Deviation 0.0467
|
PRIMARY outcome
Timeframe: Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272Population: The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics.
Outcome measures
| Measure |
Cohort 1: TAK-272
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 1.
|
Cohort 1: TAK-272 + Itraconazole
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
|---|---|---|
|
Cmax: Maximum Observed Plasma Concentration for Digoxin in Cohort 2
|
1.212 ng/mL
Standard Deviation 0.58104
|
1.635 ng/mL
Standard Deviation 0.70089
|
PRIMARY outcome
Timeframe: Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272Population: The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics.
Outcome measures
| Measure |
Cohort 1: TAK-272
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 1.
|
Cohort 1: TAK-272 + Itraconazole
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
|---|---|---|
|
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Digoxin in Cohort 2
|
15.49 ng*hr/mL
Standard Deviation 4.4007
|
15.79 ng*hr/mL
Standard Deviation 4.2495
|
PRIMARY outcome
Timeframe: Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272Population: The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics.
Outcome measures
| Measure |
Cohort 1: TAK-272
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 1.
|
Cohort 1: TAK-272 + Itraconazole
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
|---|---|---|
|
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Digoxin in Cohort 2
|
9.191 ng*hr/mL
Standard Deviation 2.6150
|
10.61 ng*hr/mL
Standard Deviation 2.6705
|
PRIMARY outcome
Timeframe: Day 1 and Day 7: pre-dose and at multiple time-points (upto 48 hours) postdose; Day 1 for Cohort 2: Digoxin and Day 7 for Cohort 2: Digoxin + TAK-272Population: The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics.
Outcome measures
| Measure |
Cohort 1: TAK-272
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 1.
|
Cohort 1: TAK-272 + Itraconazole
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
|---|---|---|
|
Urinary Excretion Ratio of Digoxin From 0 to 48 Hours Postdose in Cohort 2
|
31.391 percentage of dose
Standard Deviation 8.4376
|
35.983 percentage of dose
Standard Deviation 7.7691
|
PRIMARY outcome
Timeframe: Day 1 and Day 7: pre-dose and at multiple time-points (upto 24 hours) postdose; Day 1 for Cohort 2: Midazolam and Day 7 for Cohort 2: Midazolam + TAK-272Population: The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics.
Outcome measures
| Measure |
Cohort 1: TAK-272
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 1.
|
Cohort 1: TAK-272 + Itraconazole
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
|---|---|---|
|
Cmax: Maximum Observed Plasma Concentration for Midazolam and 1'Hydroxymidazolam in Cohort 2
Midazolam
|
10.02 ng/mL
Standard Deviation 3.6198
|
12.37 ng/mL
Standard Deviation 5.0127
|
|
Cmax: Maximum Observed Plasma Concentration for Midazolam and 1'Hydroxymidazolam in Cohort 2
1'hydroxymidazolam
|
4.813 ng/mL
Standard Deviation 1.8090
|
4.270 ng/mL
Standard Deviation 1.1195
|
PRIMARY outcome
Timeframe: Day 1 and Day 7: pre-dose and at multiple time-points (upto 24 hours) postdose; Day 1 for Cohort 2: Midazolam and Day 7 for Cohort 2: Midazolam + TAK-272Population: The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics.
Outcome measures
| Measure |
Cohort 1: TAK-272
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 1.
|
Cohort 1: TAK-272 + Itraconazole
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
|---|---|---|
|
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam and 1'Hydroxymidazolam in Cohort 2
Midazolam
|
27.11 ng*hr/mL
Standard Deviation 11.362
|
38.55 ng*hr/mL
Standard Deviation 18.588
|
|
AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam and 1'Hydroxymidazolam in Cohort 2
1'hydroxymidazolam
|
13.00 ng*hr/mL
Standard Deviation 4.0705
|
14.06 ng*hr/mL
Standard Deviation 4.5131
|
PRIMARY outcome
Timeframe: Day 1 and Day 7: pre-dose and at multiple time-points (upto 24 hours) postdose; Day 1 for Cohort 2: Midazolam and Day 7 for Cohort 2: Midazolam + TAK-272Population: The pharmacokinetic analysis set was defined as the set of participants treated with the study drug that had no significant protocol deviation, satisfied the minimum protocol provisions, and could be evaluated for pharmacokinetics.
Outcome measures
| Measure |
Cohort 1: TAK-272
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 1.
|
Cohort 1: TAK-272 + Itraconazole
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
|---|---|---|
|
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Midazolam and 1'Hydroxymidazolam in Cohort 2
Midazolam
|
26.77 ng*hr/mL
Standard Deviation 11.343
|
38.16 ng*hr/mL
Standard Deviation 18.205
|
|
AUC(0-tlqc): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Midazolam and 1'Hydroxymidazolam in Cohort 2
1'hydroxymidazolam
|
12.49 ng*hr/mL
Standard Deviation 3.7079
|
13.25 ng*hr/mL
Standard Deviation 3.3695
|
PRIMARY outcome
Timeframe: Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15Population: The safety analysis set was defined as all participants who received at least one dose of study drug.
Outcome measures
| Measure |
Cohort 1: TAK-272
n=16 Participants
TAK-272 40 mg, tablet, orally, once on Day 1.
|
Cohort 1: TAK-272 + Itraconazole
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
|---|---|---|
|
Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
|
10 participants
|
7 participants
|
PRIMARY outcome
Timeframe: Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15Population: The safety analysis set was defined as all participants who received at least one dose of study drug.
Outcome measures
| Measure |
Cohort 1: TAK-272
n=16 Participants
TAK-272 40 mg, tablet, orally, once on Day 1.
|
Cohort 1: TAK-272 + Itraconazole
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
|---|---|---|
|
Number of Participants With TEAEs Related to Vital Signs
Blood pressure decreased
|
1 participants
|
0 participants
|
|
Number of Participants With TEAEs Related to Vital Signs
Hypotension
|
2 participants
|
0 participants
|
|
Number of Participants With TEAEs Related to Vital Signs
Heart rate increased
|
0 participants
|
1 participants
|
PRIMARY outcome
Timeframe: Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15Population: The safety analysis set was defined as all participants who received at least one dose of study drug.
Outcome measures
| Measure |
Cohort 1: TAK-272
n=16 Participants
TAK-272 40 mg, tablet, orally, once on Day 1.
|
Cohort 1: TAK-272 + Itraconazole
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
|---|---|---|
|
Number of Participants With TEAEs Related to Body Weight
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15Population: The safety analysis set was defined as all participants who received at least one dose of study drug.
Number of participants who had ECG findings changed from "within normal limit" or "abnormal, clinically significant" to "abnormal and clinically significant" after study drug administration.
Outcome measures
| Measure |
Cohort 1: TAK-272
n=16 Participants
TAK-272 40 mg, tablet, orally, once on Day 1.
|
Cohort 1: TAK-272 + Itraconazole
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
|---|---|---|
|
Number of Participants Who Had Clinically Significant Changes From Baseline in 12-lead Electrocardiograms
|
0 participants
|
0 participants
|
PRIMARY outcome
Timeframe: Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15Population: The safety analysis set was defined as all participants who received at least one dose of study drug.
Outcome measures
| Measure |
Cohort 1: TAK-272
n=16 Participants
TAK-272 40 mg, tablet, orally, once on Day 1.
|
Cohort 1: TAK-272 + Itraconazole
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
|---|---|---|
|
Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis
Alanine aminotransferase increased
|
2 participants
|
1 participants
|
|
Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis
Blood creatine phosphokinase increased
|
1 participants
|
0 participants
|
|
Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis
Blood triglycerides increased
|
0 participants
|
1 participants
|
|
Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis
Urine ketone body present
|
0 participants
|
1 participants
|
PRIMARY outcome
Timeframe: Cohort 2: Baseline up to Day 15Population: The safety analysis set was defined as all participants who received at least one dose of study drug.
Outcome measures
| Measure |
Cohort 1: TAK-272
n=18 Participants
TAK-272 40 mg, tablet, orally, once on Day 1.
|
Cohort 1: TAK-272 + Itraconazole
TAK-272 40 mg, tablet, orally, once on Day 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
|---|---|---|
|
Number of Participants With Clinically Significant Change From Baseline in Continuous Pulse Oximetry (SpO2) in Cohort 2
|
0 participants
|
—
|
Adverse Events
Cohort 1: TAK-272 + Itraconazole
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Cohort 2: Midazolam + Digoxin + TAK-272
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cohort 1: TAK-272 + Itraconazole
n=16 participants at risk
TAK-272 40 milligram (mg), tablet, orally, once on Day 1 and 10, followed by Itraconazole 200 mg, solution, orally, twice on Day 4, further followed by Itraconazole 200 mg, solution, orally, once from Day 5 to 12.
|
Cohort 2: Midazolam + Digoxin + TAK-272
n=18 participants at risk
Midazolam 2 mg, syrup, and Digoxin 0.25 mg, tablet, orally, once on Day 1 and 7, followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8.
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
6.2%
1/16 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
5.6%
1/18 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Injury, poisoning and procedural complications
Procedural pain
|
6.2%
1/16 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/18 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Investigations
Alanine aminotransferase increased
|
12.5%
2/16 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
5.6%
1/18 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Investigations
Blood creatine phosphokinase increased
|
6.2%
1/16 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/18 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Investigations
Blood pressure decreased
|
6.2%
1/16 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/18 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Investigations
Blood triglycerides increased
|
0.00%
0/16 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
5.6%
1/18 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Investigations
Heart rate increased
|
0.00%
0/16 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
5.6%
1/18 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Investigations
Urine ketone body present
|
0.00%
0/16 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
5.6%
1/18 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Dizziness
|
6.2%
1/16 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
11.1%
2/18 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Dizziness postural
|
6.2%
1/16 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
5.6%
1/18 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Nervous system disorders
Somnolence
|
0.00%
0/16 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
5.6%
1/18 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.2%
1/16 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/18 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
|
Vascular disorders
Hypotension
|
12.5%
2/16 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
0.00%
0/18 • Collection of AEs commenced from the time that the participant was first administered study drug (Day 1) until the follow-up examination (Day 19 for Cohort 1, Day 15 for Cohort 2)
At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee No publication related to study results will be made without Sponsor's prior written approval. Any proposed publication or presentation will be submitted to Sponsor for review 60 days in advance of publication. Institution will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for an additional 60 days to preserve intellectual property.
- Publication restrictions are in place
Restriction type: OTHER