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Trial record 80 of 205 for:    SPORANOX I.V. OR ITRACONAZOLE OR ONMEL OR SPORANOX-PULSE OR Sporanos OR R 51,211 OR SPORANOX

Drug-Drug Interaction Study Between TAK-272 and Itraconazole, Digoxin or Midazolam

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02370615
Recruitment Status : Completed
First Posted : February 25, 2015
Results First Posted : May 23, 2016
Last Update Posted : May 23, 2016
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Japanese Healthy Adult Males
Interventions Drug: TAK-272
Drug: Digoxin
Drug: Itraconazole
Drug: Midazolam
Enrollment 34
Recruitment Details Participants took part in the study at 1 investigative site in Japan from 25-February-2015 to 16-April-2015.
Pre-assignment Details 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.
Arm/Group Title Cohort 1: TAK-272 + Itraconazole Cohort 2: Midazolam + Digoxin + TAK-272
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 16 18
Completed 15 18
Not Completed 1 0
Reason Not Completed
Adverse Event             1             0
Arm/Group Title Cohort 1: TAK-272 + Itraconazole Cohort 2: Midazolam + Digoxin + TAK-272 Total
Hide Arm/Group Description 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. 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 of all reporting groups
Overall Number of Baseline Participants 15 18 33
Hide Baseline Analysis Population Description
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.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants 18 participants 33 participants
26.8  (4.11) 25.3  (4.44) 26.0  (4.30)
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Male Number Analyzed 15 participants 18 participants 33 participants
15 18 33
Smoking Classification  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants 18 participants 33 participants
Never smoked 12 12 24
Current smoker 1 1 2
Ex-smoker 2 5 7
Alcohol Classification  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants 18 participants 33 participants
Drinks a few days per week 5 2 7
Drinks a few days per month 5 5 10
Does not drink 5 11 16
Caffeine Classification  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants 18 participants 33 participants
Caffeine consumption 7 6 13
No caffeine consumption 8 12 20
1.Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for TAK 272F and TAK 272-Metabolite (M-I) in Cohort 1
Hide Description [Not Specified]
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohort 1: TAK-272 Cohort 1: TAK-272 + Itraconazole
Hide Arm/Group Description:
TAK-272 40 mg, tablet, orally, once on Day 1.
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.
Overall Number of Participants Analyzed 15 15
Geometric Mean (Standard Deviation)
Unit of Measure: nanogram per milliliter (ng/mL)
TAK 272 387.8  (286.18) 780.3  (258.45)
TAK 272-M-I 10.02  (7.1545) 0.9550  (0.55302)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: TAK-272, Cohort 1: TAK-272 + Itraconazole
Comments Analysis for TAK 272F
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio (Day 10/Day 1)
Estimated Value 2.012
Confidence Interval (2-Sided) 90%
1.632 to 2.481
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 1: TAK-272, Cohort 1: TAK-272 + Itraconazole
Comments Analysis for TAK 272-M-I
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio (Day 10/Day 1)
Estimated Value 0.089
Confidence Interval (2-Sided) 90%
0.064 to 0.123
Estimation Comments [Not Specified]
2.Primary Outcome
Title 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
Hide Description [Not Specified]
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohort 1: TAK-272 Cohort 1: TAK-272 + Itraconazole
Hide Arm/Group Description:
TAK-272 40 mg, tablet, orally, once on Day 1.
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.
Overall Number of Participants Analyzed 15 15
Geometric Mean (Standard Deviation)
Unit of Measure: nanogram hours per milliliter (ng*hr/mL)
TAK 272 1861  (731.14) 9098  (2809.8)
TAK 272-M-I 46.53  (19.347) 9.373  (8.9682)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: TAK-272, Cohort 1: TAK-272 + Itraconazole
Comments Analysis for TAK 272F
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio (Day 10/Day 1)
Estimated Value 4.888
Confidence Interval (2-Sided) 90%
4.137 to 5.777
Estimation Comments [Not Specified]
3.Primary Outcome
Title 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
Hide Description [Not Specified]
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohort 1: TAK-272 Cohort 1: TAK-272 + Itraconazole
Hide Arm/Group Description:
TAK-272 40 mg, tablet, orally, once on Day 1.
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.
Overall Number of Participants Analyzed 15 15
Geometric Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
TAK 272 1842  (728.15) 8659  (2596.7)
TAK 272-M-I 38.34  (16.944) 0.9092  (1.5900)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: TAK-272, Cohort 1: TAK-272 + Itraconazole
Comments Analysis for TAK 272F
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio (Day 10/Day 1)
Estimated Value 4.702
Confidence Interval (2-Sided) 90%
3.969 to 5.569
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 1: TAK-272, Cohort 1: TAK-272 + Itraconazole
Comments Analysis for TAK 272-M-I
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio (Day 10/Day 1)
Estimated Value 0.023
Confidence Interval (2-Sided) 90%
0.012 to 0.045
Estimation Comments [Not Specified]
4.Primary Outcome
Title Cumulative Urinary Excretion Ratio of TAK 272F and TAK 272-M-I From 0 to 72 Hours Postdose in Cohort 1
Hide Description [Not Specified]
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohort 1: TAK-272 Cohort 1: TAK-272 + Itraconazole
Hide Arm/Group Description:
TAK-272 40 mg, tablet, orally, once on Day 1.
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.
Overall Number of Participants Analyzed 15 15
Mean (Standard Deviation)
Unit of Measure: percentage of dose
TAK 272 11.523  (2.6615) 37.803  (5.4878)
TAK 272-M-I 0.556  (0.1534) 0.071  (0.0467)
5.Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for Digoxin in Cohort 2
Hide Description [Not Specified]
Time Frame 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-272
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohort 2: Digoxin Cohort 2: Digoxin + TAK-272
Hide Arm/Group Description:
Digoxin 0.25 mg, tablet, orally once on Day 1 and 7.
Digoxin 0.25 mg, tablet, orally once on Day 7, further followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8.
Overall Number of Participants Analyzed 18 18
Geometric Mean (Standard Deviation)
Unit of Measure: ng/mL
1.212  (0.58104) 1.635  (0.70089)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Digoxin, Cohort 2: Digoxin + TAK-272
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio (Day 7/Day 1)
Estimated Value 1.349
Confidence Interval (2-Sided) 90%
1.117 to 1.628
Estimation Comments [Not Specified]
6.Primary Outcome
Title AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Digoxin in Cohort 2
Hide Description [Not Specified]
Time Frame 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-272
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohort 2: Digoxin Cohort 2: Digoxin + TAK-272
Hide Arm/Group Description:
Digoxin 0.25 mg, tablet, orally once on Day 1 and 7.
Digoxin 0.25 mg, tablet, orally once on Day 7, further followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8.
Overall Number of Participants Analyzed 18 18
Geometric Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
15.49  (4.4007) 15.79  (4.2495)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Digoxin, Cohort 2: Digoxin + TAK-272
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio (Day 7/Day 1)
Estimated Value 1.020
Confidence Interval (2-Sided) 90%
0.919 to 1.131
Estimation Comments [Not Specified]
7.Primary Outcome
Title 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
Hide Description [Not Specified]
Time Frame 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-272
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohort 2: Digoxin Cohort 2: Digoxin + TAK-272
Hide Arm/Group Description:
Digoxin 0.25 mg, tablet, orally once on Day 1 and 7.
Digoxin 0.25 mg, tablet, orally once on Day 7, further followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8.
Overall Number of Participants Analyzed 18 18
Geometric Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
9.191  (2.6150) 10.61  (2.6705)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Digoxin, Cohort 2: Digoxin + TAK-272
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio (Day 7/Day 1)
Estimated Value 1.155
Confidence Interval (2-Sided) 90%
1.035 to 1.289
Estimation Comments [Not Specified]
8.Primary Outcome
Title Urinary Excretion Ratio of Digoxin From 0 to 48 Hours Postdose in Cohort 2
Hide Description [Not Specified]
Time Frame 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-272
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohort 2: Digoxin Cohort 2: Digoxin + TAK-272
Hide Arm/Group Description:
Digoxin 0.25 mg, tablet, orally once on Day 1 and 7.
Digoxin 0.25 mg, tablet, orally once on Day 7, further followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8.
Overall Number of Participants Analyzed 18 18
Mean (Standard Deviation)
Unit of Measure: percentage of dose
31.391  (8.4376) 35.983  (7.7691)
9.Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for Midazolam and 1’Hydroxymidazolam in Cohort 2
Hide Description [Not Specified]
Time Frame 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-272
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohort 2: Midazolam Cohort 2: Midazolam + TAK-272
Hide Arm/Group Description:
Midazolam 2 mg, syrup, orally, once on Day 1.
Midazolam 2 mg, syrup, orally, once on Day 7, followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8.
Overall Number of Participants Analyzed 18 18
Geometric Mean (Standard Deviation)
Unit of Measure: ng/mL
Midazolam 10.02  (3.6198) 12.37  (5.0127)
1’hydroxymidazolam 4.813  (1.8090) 4.270  (1.1195)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Midazolam, Cohort 2: Midazolam + TAK-272
Comments Analysis for Midazolam
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio (Day 7/Day 1)
Estimated Value 1.235
Confidence Interval (2-Sided) 90%
1.100 to 1.387
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2: Midazolam, Cohort 2: Midazolam + TAK-272
Comments Analysis for 1’Hydroxymidazolam
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio (Day 7/Day 1)
Estimated Value 0.887
Confidence Interval (2-Sided) 90%
0.781 to 1.008
Estimation Comments [Not Specified]
10.Primary Outcome
Title AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Midazolam and 1’Hydroxymidazolam in Cohort 2
Hide Description [Not Specified]
Time Frame 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-272
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohort 2: Midazolam Cohort 2: Midazolam + TAK-272
Hide Arm/Group Description:
Midazolam 2 mg, syrup, orally, once on Day 1.
Midazolam 2 mg, syrup, orally, once on Day 7, followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8.
Overall Number of Participants Analyzed 18 18
Geometric Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
Midazolam 27.11  (11.362) 38.55  (18.588)
1’hydroxymidazolam 13.00  (4.0705) 14.06  (4.5131)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Midazolam, Cohort 2: Midazolam + TAK-272
Comments Analysis for Midazolam
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio (Day 7/Day 1)
Estimated Value 1.422
Confidence Interval (2-Sided) 90%
1.290 to 1.568
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2: Midazolam, Cohort 2: Midazolam + TAK-272
Comments Analysis for 1’Hydroxymidazolam
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio (Day 7/Day 1)
Estimated Value 1.081
Confidence Interval (2-Sided) 90%
1.008 to 1.160
Estimation Comments [Not Specified]
11.Primary Outcome
Title 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
Hide Description [Not Specified]
Time Frame 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-272
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Cohort 2: Midazolam Cohort 2: Midazolam + TAK-272
Hide Arm/Group Description:
Midazolam 2 mg, syrup, orally, once on Day 1.
Midazolam 2 mg, syrup, orally, once on Day 7, followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8.
Overall Number of Participants Analyzed 18 18
Geometric Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
Midazolam 26.77  (11.343) 38.16  (18.205)
1’hydroxymidazolam 12.49  (3.7079) 13.25  (3.3695)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 2: Midazolam, Cohort 2: Midazolam + TAK-272
Comments Analysis for Midazolam
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio (Day 7/Day 1)
Estimated Value 1.425
Confidence Interval (2-Sided) 90%
1.291 to 1.574
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Cohort 2: Midazolam, Cohort 2: Midazolam + TAK-272
Comments Analysis for 1’Hydroxymidazolam
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Geometric Mean Ratio (Day 7/Day 1)
Estimated Value 1.061
Confidence Interval (2-Sided) 90%
0.986 to 1.143
Estimation Comments [Not Specified]
12.Primary Outcome
Title Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Hide Description [Not Specified]
Time Frame Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set was defined as all participants who received at least one dose of study drug.
Arm/Group Title Cohort 1: TAK-272 + Itraconazole Cohort 2: Midazolam + Digoxin + TAK-272
Hide Arm/Group Description:
TAK-272 40 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.
Midazolam 2 mg, syrup, orally, once on Day 1 and 7, followed by Digoxin 0.25 mg, tablet, orally once on Day 1 and 7, further followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8.
Overall Number of Participants Analyzed 16 18
Measure Type: Number
Unit of Measure: participants
10 7
13.Primary Outcome
Title Number of Participants With TEAEs Related to Vital Signs
Hide Description [Not Specified]
Time Frame Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set was defined as all participants who received at least one dose of study drug.
Arm/Group Title Cohort 1: TAK-272 + Itraconazole Cohort 2: Midazolam + Digoxin + TAK-272
Hide Arm/Group Description:
TAK-272 40 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.
Midazolam 2 mg, syrup, orally, once on Day 1 and 7, followed by Digoxin 0.25 mg, tablet, orally once on Day 1 and 7, further followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8.
Overall Number of Participants Analyzed 16 18
Measure Type: Number
Unit of Measure: participants
Blood pressure decreased 1 0
Hypotension 2 0
Heart rate increased 0 1
14.Primary Outcome
Title Number of Participants With TEAEs Related to Body Weight
Hide Description [Not Specified]
Time Frame Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set was defined as all participants who received at least one dose of study drug.
Arm/Group Title Cohort 1: TAK-272 + Itraconazole Cohort 2: Midazolam + Digoxin + TAK-272
Hide Arm/Group Description:
TAK-272 40 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.
Midazolam 2 mg, syrup, orally, once on Day 1 and 7, followed by Digoxin 0.25 mg, tablet, orally once on Day 1 and 7, further followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8.
Overall Number of Participants Analyzed 16 18
Measure Type: Number
Unit of Measure: participants
0 0
15.Primary Outcome
Title Number of Participants Who Had Clinically Significant Changes From Baseline in 12-lead Electrocardiograms
Hide Description 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.
Time Frame Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set was defined as all participants who received at least one dose of study drug.
Arm/Group Title Cohort 1: TAK-272 + Itraconazole Cohort 2: Midazolam + Digoxin + TAK-272
Hide Arm/Group Description:
TAK-272 40 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.
Midazolam 2 mg, syrup, orally, once on Day 1 and 7, followed by Digoxin 0.25 mg, tablet, orally once on Day 1 and 7, further followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8.
Overall Number of Participants Analyzed 16 18
Measure Type: Number
Unit of Measure: participants
0 0
16.Primary Outcome
Title Number of Participants With TEAEs Categorized Into Investigations System Organ Class (SOC) Related to Chemistry, Hematology or Urinalysis
Hide Description [Not Specified]
Time Frame Cohort 1: Baseline up to Day 19; Cohort 2: Baseline up to Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set was defined as all participants who received at least one dose of study drug.
Arm/Group Title Cohort 1: TAK-272 + Itraconazole Cohort 2: Midazolam + Digoxin + TAK-272
Hide Arm/Group Description:
TAK-272 40 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.
Midazolam 2 mg, syrup, orally, once on Day 1 and 7, followed by Digoxin 0.25 mg, tablet, orally once on Day 1 and 7, further followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8.
Overall Number of Participants Analyzed 16 18
Measure Type: Number
Unit of Measure: participants
Alanine aminotransferase increased 2 1
Blood creatine phosphokinase increased 1 0
Blood triglycerides increased 0 1
Urine ketone body present 0 1
17.Primary Outcome
Title Number of Participants With Clinically Significant Change From Baseline in Continuous Pulse Oximetry (SpO2) in Cohort 2
Hide Description [Not Specified]
Time Frame Cohort 2: Baseline up to Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
The safety analysis set was defined as all participants who received at least one dose of study drug.
Arm/Group Title Cohort 2: Midazolam + Digoxin + TAK-272
Hide Arm/Group Description:
Midazolam 2 mg, syrup, orally, once on Day 1 and 7, followed by Digoxin 0.25 mg, tablet, orally once on Day 1 and 7, further followed by TAK-272 80 mg, tablet, orally, once from Day 3 to 8.
Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: participants
0
Time Frame 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)
Adverse Event Reporting Description 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.
 
Arm/Group Title Cohort 1: TAK-272 + Itraconazole Cohort 2: Midazolam + Digoxin + TAK-272
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Cohort 1: TAK-272 + Itraconazole Cohort 2: Midazolam + Digoxin + TAK-272
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Cohort 1: TAK-272 + Itraconazole Cohort 2: Midazolam + Digoxin + TAK-272
Affected / at Risk (%) Affected / at Risk (%)
Total   0/16 (0.00%)   0/18 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Cohort 1: TAK-272 + Itraconazole Cohort 2: Midazolam + Digoxin + TAK-272
Affected / at Risk (%) Affected / at Risk (%)
Total   10/16 (62.50%)   7/18 (38.89%) 
Infections and infestations     
Nasopharyngitis  1  1/16 (6.25%)  1/18 (5.56%) 
Injury, poisoning and procedural complications     
Procedural pain  1  1/16 (6.25%)  0/18 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  2/16 (12.50%)  1/18 (5.56%) 
Blood creatine phosphokinase increased  1  1/16 (6.25%)  0/18 (0.00%) 
Blood pressure decreased  1  1/16 (6.25%)  0/18 (0.00%) 
Blood triglycerides increased  1  0/16 (0.00%)  1/18 (5.56%) 
Heart rate increased  1  0/16 (0.00%)  1/18 (5.56%) 
Urine ketone body present  1  0/16 (0.00%)  1/18 (5.56%) 
Nervous system disorders     
Dizziness  1  1/16 (6.25%)  2/18 (11.11%) 
Dizziness postural  1  1/16 (6.25%)  1/18 (5.56%) 
Somnolence  1  0/16 (0.00%)  1/18 (5.56%) 
Respiratory, thoracic and mediastinal disorders     
Oropharyngeal pain  1  1/16 (6.25%)  0/18 (0.00%) 
Vascular disorders     
Hypotension  1  2/16 (12.50%)  0/18 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (18.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02370615     History of Changes
Other Study ID Numbers: TAK-272/CPH-011
U1111-1167-0017 ( Registry Identifier: WHO )
JapicCTI-152810 ( Registry Identifier: JapicCTI )
First Submitted: February 18, 2015
First Posted: February 25, 2015
Results First Submitted: April 14, 2016
Results First Posted: May 23, 2016
Last Update Posted: May 23, 2016