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A Study to Evaluate the Effect of the Potent Cytochrome P-450 3A4 (CYP3A4) Inhibitor Itraconazole on the Pharmacokinetics (PK) of TAK-954 in Healthy Adult Participants

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ClinicalTrials.gov Identifier: NCT03173170
Recruitment Status : Completed
First Posted : June 1, 2017
Results First Posted : January 15, 2019
Last Update Posted : January 15, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition Healthy Participants
Interventions Drug: TAK-954
Drug: Itraconazole
Enrollment 10
Recruitment Details Participants took part in the study at 1 investigative site in United States from 31 May 2017 to 24 July 2017.
Pre-assignment Details Healthy participants were enrolled in this single sequence 2-period crossover study to receive TAK-954 0.2 milligram (mg) in Intervention Period 1 followed by itraconazole 200 mg + TAK-954 0.2 mg in Intervention Period 2.
Arm/Group Title TAK-954 0.2 mg + Itraconazole 200 mg and TAK-954 0.2mg
Hide Arm/Group Description TAK-954 0.2 mg, infusion, intravenously, once on Day 1 of First Intervention Period, followed by a minimum of 7-day washout period, further followed by itraconazole 200 mg, capsule, orally, once daily on Days 1 to 8 along with TAK-954 0.2 mg, infusion, intravenously on Day 4 of Second Intervention Period.
Period Title: First Intervention Period (6 Days)
Started 10
Completed 10
Not Completed 0
Period Title: Washout Period (at Least 7 Days)
Started 10
Completed 10
Not Completed 0
Period Title: Intervention Period 2 (9 Days)
Started 10
Completed 10
Not Completed 0
Arm/Group Title TAK-954 0.2 mg + Itraconazole 200 mg and TAK-954 0.2mg
Hide Arm/Group Description TAK-954 0.2 mg, infusion, intravenously, once on Day 1 of First Intervention Period, followed by a minimum of 7-day washout period, further followed by itraconazole 200 mg, capsule, orally, once daily on Days 1 to 8 along with TAK-954 0.2 mg, infusion, intravenously on Day 4 of Second Intervention Period.
Overall Number of Baseline Participants 10
Hide Baseline Analysis Population Description
The safety analysis set included all participants who were randomized and received at least 1 dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 10 participants
34.7  (10.34)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Female
1
  10.0%
Male
9
  90.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
Hispanic or Latino
0
   0.0%
Not Hispanic or Latino
10
 100.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
2
  20.0%
White
8
  80.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 10 participants
10
 100.0%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilogram (kg)
Number Analyzed 10 participants
73.72  (11.534)
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeter (cm)
Number Analyzed 10 participants
174.4  (10.17)
Body mass index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kilogram per square meter (kg/m^2)
Number Analyzed 10 participants
24.2  (2.90)
1.Primary Outcome
Title Cmax: Maximum Observed Plasma Concentration for TAK-954
Hide Description [Not Specified]
Time Frame TAK-954 0.2 mg: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose; Itraconazole 200 mg and TAK-954 0.2 mg: Day 4 pre-dose and at multiple time points (up to 120 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The pharmacokinetic (PK) set included all participants who received at least 1 dose of study drug and had at least 1 measurable plasma concentration.
Arm/Group Title TAK-954 0.2 mg Itraconazole 200 mg and TAK-954 0.2 mg
Hide Arm/Group Description:
TAK-954 0.2 mg, infusion, intravenously, once on Day 1 of First Intervention Period.
Itraconazole 200 mg, capsule, orally, once daily on Days 1 to 8 along with TAK-954 0.2 mg, infusion, intravenously on Day 4 of Second Intervention Period.
Overall Number of Participants Analyzed 10 10
Geometric Mean (Standard Deviation)
Unit of Measure: nanogram/milliliter (ng/mL)
2.642  (0.4426) 2.840  (0.6497)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TAK-954 0.2 mg, Itraconazole 200 mg and TAK-954 0.2 mg
Comments A paired t-test on the natural log-transformed parameters was performed. The means and difference of means for the log-transformed parameters were exponentiated to obtain the point estimates of the itraconazole effect and 90 percent (%) confidence intervals (CIs).
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean ratio
Estimated Value 1.0622
Confidence Interval (2-Sided) 90%
0.9569 to 1.1792
Estimation Comments [Not Specified]
2.Primary Outcome
Title AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-954
Hide Description [Not Specified]
Time Frame TAK-954 0.2 mg: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose; Itraconazole 200 mg and TAK-954 0.2mg: Day 1 pre-dose and at multiple time points (up to 120 hours) post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The PK set included all participants who received at least 1 dose of study drug and had at least 1 measurable plasma concentration. PK analysis set where Day 1 and 4 assessments were available.
Arm/Group Title TAK-954 0.2 mg Itraconazole 200 mg and TAK-954 0.2mg
Hide Arm/Group Description:
TAK-954 0.2 mg, infusion, intravenously, once on Day 1 of First Intervention Period.
Itraconazole 200 mg, capsule, orally, once daily on Days 1 to 8 along with TAK-954 0.2 mg, infusion, intravenously on Day 4 of Second Intervention Period.
Overall Number of Participants Analyzed 10 10
Geometric Mean (Standard Deviation)
Unit of Measure: hour*nanogram per milliliter (hr*ng/mL)
28.59  (6.550) 43.15  (10.265)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TAK-954 0.2 mg, Itraconazole 200 mg and TAK-954 0.2mg
Comments A paired t-test on the natural log-transformed parameters was performed. The means and difference of means for the log-transformed parameters were exponentiated to obtain the point estimates of the itraconazole effect and 90% CIs.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean ratio
Estimated Value 1.4892
Confidence Interval (2-Sided) 90%
1.3851 to 1.6012
Estimation Comments [Not Specified]
Time Frame Treatment-emergent adverse events are adverse events that started after the first dose of study drug up to Day 9 of Second Intervention Period
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 TAK-954 0.2 mg Itraconazole 200 mg Itraconazole 200 mg and TAK-954 0.2 mg
Hide Arm/Group Description TAK-954 0.2 mg, infusion, intravenously, once on Day 1 of First Intervention Period. Itraconazole 200 mg, capsule, orally, once daily on Days 1 to 3 of Second Intervention Period. Itraconazole 200 mg, capsule, orally, once daily on Days 4 to 8 along with TAK-954 0.2 mg, infusion, intravenously on Day 4 of Second Intervention Period.
All-Cause Mortality
TAK-954 0.2 mg Itraconazole 200 mg Itraconazole 200 mg and TAK-954 0.2 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/10 (0.00%)   0/10 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
TAK-954 0.2 mg Itraconazole 200 mg Itraconazole 200 mg and TAK-954 0.2 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/10 (0.00%)   0/10 (0.00%)   0/10 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
TAK-954 0.2 mg Itraconazole 200 mg Itraconazole 200 mg and TAK-954 0.2 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/10 (30.00%)   0/10 (0.00%)   1/10 (10.00%) 
Gastrointestinal disorders       
Anal incontinence  1  1/10 (10.00%)  0/10 (0.00%)  0/10 (0.00%) 
Diarrhoea  1  1/10 (10.00%)  0/10 (0.00%)  0/10 (0.00%) 
Nervous system disorders       
Headache  1  3/10 (30.00%)  0/10 (0.00%)  1/10 (10.00%) 
Presyncope  1  1/10 (10.00%)  0/10 (0.00%)  0/10 (0.00%) 
1
Term from vocabulary, MedDRA (20.0)
Indicates events were collected by systematic assessment
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.
Research Organization shall not publish any articles or papers nor make any presentations, nor assist any other person in publishing any articles or papers or in making any presentations relating or referring to the Study or any results, data or insights from or any data, information or materials obtained or generated in the performance of its obligations without the prior written consent of Takeda, which consent may be granted or withheld in Takeda’s sole discretion.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Takeda
Phone: +1-877-825-3327
EMail: trialdisclosures@takeda.com
Layout table for additonal information
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT03173170     History of Changes
Other Study ID Numbers: TAK-954-1004
2017-000713-22 ( EudraCT Number )
U1111-1195-7682 ( Registry Identifier: WHO )
First Submitted: May 30, 2017
First Posted: June 1, 2017
Results First Submitted: July 20, 2018
Results First Posted: January 15, 2019
Last Update Posted: January 15, 2019