A Study to Evaluate the Effect of Single-Dose Intravenous Rifampin as a Prototypic Inhibitor of Organic Anion Transporting Polypeptide (OATP) 1B1 and OATP1B3 on the Single-Dose Pharmacokinetics (PK) of Oral TAK-906 in Healthy Adult Participants

Sponsor
Millennium Pharmaceuticals, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT04121078
Collaborator
(none)
12
Enrollment
1
Location
2
Arms
1.1
Actual Duration (Months)
11.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effect of single dose intravenous rifampin on the single-dose PK of orally administered TAK-906.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1

Detailed Description

The drug being tested in this study is called TAK-906. TAK-906 is being tested to evaluate the effect of single dose intravenous rifampin on the single-dose PK of oral TAK-906 in healthy adult participants.

The study will enroll approximately 12 participants. Participants will be randomly assigned to one of the two treatment sequences AB or BA:

  • Sequence AB: TAK-906 25 mg, followed by a washout period of at least 7 days, then Rifampin 600 mg and TAK-906 25 mg

  • Sequence BA: Rifampin 600 mg and TAK-906 25 mg, followed by a washout period of at least 7 days, then TAK-906 25 mg

This single center trial will be conducted in the United States. The overall time to participate in this study is 49 Days. All participants will make final visit 14 days after receiving their last dose of study drug for follow up assessment.

Study Design

Study Type:
Interventional
Actual Enrollment :
12 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
A Phase 1, Open-Label, Randomized, Two-Way Crossover Study to Evaluate the Effect of Single-Dose Intravenous Rifampin as a Prototypic Inhibitor of OATP1B1 and OATP1B3 on the Single-Dose Pharmacokinetics of Oral TAK-906 in Healthy Adult Subjects
Actual Study Start Date :
Oct 15, 2019
Actual Primary Completion Date :
Nov 4, 2019
Actual Study Completion Date :
Nov 16, 2019

Arms and Interventions

ArmIntervention/Treatment
Experimental: Sequence AB: TAK-906 25 mg + TAK-906 25 mg and Rifampin 600 mg

TAK-906 25 milligram (mg) (Treatment A), capsule, orally, once on Day 1 of Study Period 1, followed by a washout period of at least 7 days, further followed by rifampin 600 mg, infusion, once, intravenously over 30 minutes along with TAK-906 25 mg (Treatment B), capsule, orally, once immediately after the end of infusion on Day 1 of Study Period 2.

Drug: TAK-906
TAK-906 capsule.

Drug: Rifampin
Rifampin infusion.

Experimental: Sequence BA: TAK-906 25 mg and Rifampin 600 mg + TAK-906 25 mg

Rifampin 600 mg, infusion, once, intravenously over 30 minutes along with TAK-906 25 mg (Treatment B), capsule, orally, once immediately after the end of infusion on Day 1 of Study Period 1 followed by a washout period of at least 7 days, further followed by TAK-906 25 mg (Treatment A), capsule, orally, once on Day 1 of Study Period 2.

Drug: TAK-906
TAK-906 capsule.

Drug: Rifampin
Rifampin infusion.

Outcome Measures

Primary Outcome Measures

  1. Cmax: Maximum Observed Plasma Concentration for TAK-906 [Day 1: time zero and at multiple time points (up to 48 hours) post dose]

  2. AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-906 [Day 1: time zero and at multiple time points (up to 48 hours) post dose]

  3. AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-906 [Day 1: time zero and at multiple time points (up to 48 hours) post dose]

Secondary Outcome Measures

  1. Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs) [Baseline up to 14 days after the last dose of study drug in Study Period 2 (up to Day 23)]

  2. Number of Participants With Clinically Significant Change From Baseline in Vital Sign Values [Baseline up to 14 days after the last dose of study drug in Study Period 2 (up to Day 23)]

  3. Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings [Baseline up to 14 days after the last dose of study drug in Study Period 2 (up to Day 23)]

  4. Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values [Baseline up to 14 days after the last dose of study drug in Study Period 2 (up to Day 23)]

Eligibility Criteria

Criteria

Ages Eligible for Study:
19 Years to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
  1. Continuous non smoker who has not used nicotine containing products for at least 3 months prior to the first dosing and throughout the study, based on screening urine cotinine test.

  2. Body Mass Index (BMI) greater than or equal to (>=) 18.0 and less than or equal to (<=) 30.0 kilogram per square meter (kg/ m^2) at screening.

  3. Medically healthy with no clinically significant medical history, physical examination, laboratory profiles, vital signs, or ECGs, as deemed by the investigator or designee.

Exclusion Criteria:
  1. Positive urine drug or alcohol results at screening and each check in.

  2. Positive urine cotinine at screening.

  3. Positive results at screening for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV).

  4. QT interval with Fridericia's correction (QTcF) interval is >450 millisecond (msec) or ECG findings are deemed abnormal with clinical significance by the investigator or designee at screening.

  5. Estimated creatinine clearance <90 milliliter per minute (mL/min) at screening.

  6. Has been on a diet incompatible with the on-study diet, in the opinion of the investigator or designee, within the 30 days prior to the first dosing and throughout the study.

  7. Donation of blood or significant blood loss (example, approximately 500 milliliter [mL]) within 56 days prior to the first dosing.

  8. Plasma donation within 7 days prior to the first dosing.

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1CelerionLincolnNebraskaUnited States68502

Sponsors and Collaborators

  • Millennium Pharmaceuticals, Inc.

Investigators

  • Study Director: Medical Director, Millennium Pharmaceuticals, Inc.

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT04121078
Other Study ID Numbers:
  • TAK-906-1009
  • U1111-1240-6352
First Posted:
Oct 9, 2019
Last Update Posted:
Dec 9, 2020
Last Verified:
Nov 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Millennium Pharmaceuticals, Inc.
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment DetailsParticipants took part in the study at 1 investigative site in the United States from 15 October 2019 to 16 November 2019.
Pre-assignment DetailHealthy participants were enrolled in 1 of the 2 treatment sequences of this 2-period crossover study to receive TAK-906 25 milligram (mg) alone (Treatment A) and TAK-906 25 mg along with rifampin 600 mg (Treatment B).
Arm/Group TitleSequence AB: TAK-906 25 mg + TAK-906 25 mg and Rifampin 600 mgSequence BA: TAK-906 25 mg and Rifampin 600 mg + TAK-906 25 mg
Arm/Group DescriptionTAK-906 25 mg (Treatment A), capsule, orally, once on Day 1 of Study Period 1, followed by a washout period of at least 7 days, further followed by rifampin 600 mg, infusion, intravenously along with TAK-906 25 mg (Treatment B), capsule, orally, once immediately after the end of infusion on Day 1 of Study Period 2.Rifampin 600 mg, infusion, intravenously along with TAK-906 25 mg (Treatment B), capsule, orally, once immediately after the end of infusion on Day 1 of Study Period 1, followed by a washout period of at least 7 days, further followed by TAK-906 25 mg (Treatment A), capsule, orally, once on Day 1 of Study Period 2.
Period Title: Study Period 1 (1 Day)
STARTED66
COMPLETED66
NOT COMPLETED00
Period Title: Study Period 1 (1 Day)
STARTED66
COMPLETED66
NOT COMPLETED00
Period Title: Study Period 1 (1 Day)
STARTED66
COMPLETED66
NOT COMPLETED00

Baseline Characteristics

Arm/Group TitleSequence AB: TAK-906 25 mg + TAK-906 25 mg and Rifampin 600 mgSequence BA: TAK-906 25 mg and Rifampin 600 mg + TAK-906 25 mgTotal
Arm/Group DescriptionTAK-906 25 mg (Treatment A), capsule, orally, once on Day 1 of Study Period 1, followed by a washout period of at least 7 days, further followed by rifampin 600 mg, infusion, intravenously along with TAK-906 25 mg (Treatment B), capsule, orally, once immediately after the end of infusion on Day 1 of Study Period 2.Rifampin 600 mg, infusion, intravenously along with TAK-906 25 mg (Treatment B), capsule, orally, once immediately after the end of infusion on Day 1 of Study Period 1, followed by a washout period of at least 7 days, further followed by TAK-906 25 mg (Treatment A), capsule, orally, once on Day 1 of Study Period 2.Total of all reporting groups
Overall Participants6612
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
36.7
(13.47)
38.0
(8.12)
37.3
(10.63)
Sex: Female, Male (Count of Participants)
Female
1
16.7%
1
16.7%
2
16.7%
Male
5
83.3%
5
83.3%
10
83.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
0
0%
0
0%
0
0%
Not Hispanic or Latino
6
100%
6
100%
12
100%
Unknown or Not Reported
0
0%
0
0%
0
0%
Race/Ethnicity, Customized (Count of Participants)
Asian
1
16.7%
0
0%
1
8.3%
Black or African American
1
16.7%
0
0%
1
8.3%
Black or African American, White
1
16.7%
0
0%
1
8.3%
White
3
50%
6
100%
9
75%
Region of Enrollment (Count of Participants)
United States
6
100%
6
100%
12
100%
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]
74.73
(9.943)
84.25
(13.581)
79.49
(12.389)
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]
172.3
(11.74)
177.0
(9.38)
174.7
(10.42)
Body Mass Index (BMI) (kilogram per square meter (kg/m˄2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m˄2)]
25.168
(2.3720)
26.770
(1.8285)
25.969
(2.1856)

Outcome Measures

1. Primary Outcome
TitleCmax: Maximum Observed Plasma Concentration for TAK-906
Description
Time FrameDay 1: time zero and at multiple time points (up to 48 hours) post dose

Outcome Measure Data

Analysis Population Description
The pharmacokinetic (PK) set consisted of all participants who received study drug and had at least 1 measurable plasma concentration.
Arm/Group TitleTreatment A: TAK-906 25 mgTreatment B: Rifampin 600 mg and TAK-906 25 mg
Arm/Group DescriptionTAK-906 25 mg, capsule, orally, once on Day 1 of either Study Period 1 or 2.Rifampin 600 mg, infusion, intravenously along with TAK-906 25 mg, capsule, orally, once immediately after the end of infusion on Day 1 of either Study Period 1 or 2.
Measure Participants1212
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)]
14.37
(38.7)
89.62
(68.6)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment A: TAK-906 25 mg, Treatment B: Rifampin 600 mg and TAK-906 25 mg
Comments
Type of Statistical Test Equivalence
Comments Point estimate and its 90% confidence interval (CI) were calculated for Treatment B to Treatment A ratio of geometric means for Cmax based on the mixed-effect model of log-transformed Cmax with sequence, treatment, and period as fixed effects, and participant nested within sequence as a random effect. Bioequivalence was concluded if the 90% CI for the ratio of geometric means is entirely contained within 80% to 125% for Cmax. No adjustments were made for multiplicity.
Statistical Test of Hypothesisp-Value
Comments
Method
Comments
Method of EstimationEstimation ParameterGeometric Mean Ratio
Estimated Value6.24
Confidence Interval (2-Sided) 90%
4.62 to 8.42
Parameter Dispersion Type:
Value:
Estimation Comments
2. Primary Outcome
TitleAUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-906
Description
Time FrameDay 1: time zero and at multiple time points (up to 48 hours) post dose

Outcome Measure Data

Analysis Population Description
The PK set consisted of all participants who received study drug and had at least 1 measurable plasma concentration.
Arm/Group TitleTreatment A: TAK-906 25 mgTreatment B: Rifampin 600 mg and TAK-906 25 mg
Arm/Group DescriptionTAK-906 25 mg, capsule, orally, once on Day 1 of either Study Period 1 or 2.Rifampin 600 mg, infusion, intravenously along with TAK-906 25 mg, capsule, orally, once immediately after the end of infusion on Day 1 of either Study Period 1 or 2.
Measure Participants1212
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter (ng*hr/mL)]
32.68
(23.9)
168.5
(49.9)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment A: TAK-906 25 mg, Treatment B: Rifampin 600 mg and TAK-906 25 mg
Comments
Type of Statistical Test Equivalence
Comments Point estimate and its 90% CI were calculated for Treatment B to Treatment A ratio of geometric means for AUC∞ based on the mixed-effect model of log-transformed AUC∞ with sequence, treatment, and period as fixed effects, and participant nested within sequence as a random effect. Bioequivalence was concluded if the 90% CI for the ratio of geometric means is entirely contained within 80% to 125% for AUC∞. No adjustments were made for multiplicity.
Statistical Test of Hypothesisp-Value
Comments
Method
Comments
Method of EstimationEstimation ParameterGeometric Mean Ratio
Estimated Value5.16
Confidence Interval (2-Sided) 90%
4.25 to 6.25
Parameter Dispersion Type:
Value:
Estimation Comments
3. Primary Outcome
TitleAUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-906
Description
Time FrameDay 1: time zero and at multiple time points (up to 48 hours) post dose

Outcome Measure Data

Analysis Population Description
The PK set consisted of all participants who received study drug and had at least 1 measurable plasma concentration.
Arm/Group TitleTreatment A: TAK-906 25 mgTreatment B: Rifampin 600 mg and TAK-906 25 mg
Arm/Group DescriptionTAK-906 25 mg, capsule, orally, once on Day 1 of either Study Period 1 or 2.Rifampin 600 mg, infusion, intravenously along with TAK-906 25 mg, capsule, orally, once immediately after the end of infusion on Day 1 of either Study Period 1 or 2.
Measure Participants1212
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
32.32
(23.8)
168.3
(49.9)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Treatment A: TAK-906 25 mg, Treatment B: Rifampin 600 mg and TAK-906 25 mg
Comments
Type of Statistical Test Equivalence
Comments Point estimate and its 90% CI were calculated for Treatment B to Treatment A ratio of geometric means for AUClast based on the mixed-effect model of log-transformed AUClast with sequence, treatment, and period as fixed effects, and participant nested within sequence as a random effect. Bioequivalence was concluded if the 90% CI for the ratio of geometric means is entirely contained within 80% to 125% for AUClast. No adjustments were made for multiplicity.
Statistical Test of Hypothesisp-Value
Comments
Method
Comments
Method of EstimationEstimation ParameterGeometric Mean Ratio
Estimated Value5.21
Confidence Interval (2-Sided) 90%
4.29 to 6.32
Parameter Dispersion Type:
Value:
Estimation Comments
4. Secondary Outcome
TitleNumber of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Description
Time FrameBaseline up to 14 days after the last dose of study drug in Study Period 2 (up to Day 23)

Outcome Measure Data

Analysis Population Description
The safety analysis set consisted of all participants who were enrolled and received at least 1 dose of study drug.
Arm/Group TitleTreatment A: TAK-906 25 mgTreatment B: Rifampin 600 mg and TAK-906 25 mg
Arm/Group DescriptionTAK-906 25 mg, capsule, orally, once on Day 1 of either Study Period 1 or 2.Rifampin 600 mg, infusion, intravenously along with TAK-906 25 mg, capsule, orally, once immediately after the end of infusion on Day 1 of either Study Period 1 or 2.
Measure Participants1212
Count of Participants [Participants]
6
100%
2
33.3%
5. Secondary Outcome
TitleNumber of Participants With Clinically Significant Change From Baseline in Vital Sign Values
Description
Time FrameBaseline up to 14 days after the last dose of study drug in Study Period 2 (up to Day 23)

Outcome Measure Data

Analysis Population Description
The safety analysis set consisted of all participants who were enrolled and received at least 1 dose of study drug.
Arm/Group TitleTreatment A: TAK-906 25 mgTreatment B: Rifampin 600 mg and TAK-906 25 mg
Arm/Group DescriptionTAK-906 25 mg, capsule, orally, once on Day 1 of either Study Period 1 or 2.Rifampin 600 mg, infusion, intravenously along with TAK-906 25 mg, capsule, orally, once immediately after the end of infusion on Day 1 of either Study Period 1 or 2.
Measure Participants1212
Count of Participants [Participants]
0
0%
0
0%
6. Secondary Outcome
TitleNumber of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings
Description
Time FrameBaseline up to 14 days after the last dose of study drug in Study Period 2 (up to Day 23)

Outcome Measure Data

Analysis Population Description
The safety analysis set consisted of all participants who were enrolled and received at least 1 dose of study drug.
Arm/Group TitleTreatment A: TAK-906 25 mgTreatment B: Rifampin 600 mg and TAK-906 25 mg
Arm/Group DescriptionTAK-906 25 mg, capsule, orally, once on Day 1 of either Study Period 1 or 2.Rifampin 600 mg, infusion, intravenously along with TAK-906 25 mg, capsule, orally, once immediately after the end of infusion on Day 1 of either Study Period 1 or 2.
Measure Participants1212
Count of Participants [Participants]
0
0%
0
0%
7. Secondary Outcome
TitleNumber of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values
Description
Time FrameBaseline up to 14 days after the last dose of study drug in Study Period 2 (up to Day 23)

Outcome Measure Data

Analysis Population Description
The safety analysis set consisted of all participants who were enrolled and received at least 1 dose of study drug.
Arm/Group TitleTreatment A: TAK-906 25 mgTreatment B: Rifampin 600 mg and TAK-906 25 mg
Arm/Group DescriptionTAK-906 25 mg, capsule, orally, once on Day 1 of either Study Period 1 or 2.Rifampin 600 mg, infusion, intravenously along with TAK-906 25 mg, capsule, orally, once immediately after the end of infusion on Day 1 of either Study Period 1 or 2.
Measure Participants1212
Count of Participants [Participants]
0
0%
0
0%

Adverse Events

Time FrameTEAEs are adverse events (AEs) that started after the first dose of study drug and no more than 14 days after the last dose of study drug in Study Period 2 (up to Day 23)
Adverse Event Reporting Description At each visit the investigator had to document any occurrence of AEs 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 TitleTreatment A: TAK-906 25 mgTreatment B: Rifampin 600 mg and TAK-906 25 mg
Arm/Group DescriptionTAK-906 25 mg, capsule, orally, once on Day 1 of either Study Period 1 or 2.Rifampin 600 mg, infusion, intravenously along with TAK-906 25 mg, capsule, orally, once immediately after the end of infusion on Day 1 of either Study Period 1 or 2.
All Cause Mortality
Treatment A: TAK-906 25 mgTreatment B: Rifampin 600 mg and TAK-906 25 mg
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/12 (0%) 0/12 (0%)
Serious Adverse Events
Treatment A: TAK-906 25 mgTreatment B: Rifampin 600 mg and TAK-906 25 mg
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/12 (0%) 0/12 (0%)
Other (Not Including Serious) Adverse Events
Treatment A: TAK-906 25 mgTreatment B: Rifampin 600 mg and TAK-906 25 mg
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total6/12 (50%) 2/12 (16.7%)
Gastrointestinal disorders
Abdominal pain upper1/12 (8.3%) 0/12 (0%)
Nervous system disorders
Headache2/12 (16.7%) 1/12 (8.3%)
Sensory disturbance1/12 (8.3%) 0/12 (0%)
Respiratory, thoracic and mediastinal disorders
Cough0/12 (0%) 1/12 (8.3%)
Nasal congestion0/12 (0%) 1/12 (8.3%)
Sinus congestion1/12 (8.3%) 0/12 (0%)
Sneezing1/12 (8.3%) 0/12 (0%)
Skin and subcutaneous tissue disorders
Dermatitis contact1/12 (8.3%) 0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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

Name/TitleMedical Director
OrganizationTakeda
Phone+1-877-825-3327
Emailtrialdisclosures@takeda.com
Responsible Party:
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT04121078
Other Study ID Numbers:
  • TAK-906-1009
  • U1111-1240-6352
First Posted:
Oct 9, 2019
Last Update Posted:
Dec 9, 2020
Last Verified:
Nov 1, 2020