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)
• Enrollment: 12
• Location: 1
• Arms: 2
• Actual Duration (Months): 1.1
• Patients Per Site Per Month: 11.4

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 Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: TAK-906; Drug: Rifampin	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

Arm	Intervention/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

	Site	City	State	Country	Postal Code
1	Celerion	Lincoln	Nebraska	United States	68502

Sponsors and Collaborators

• Millennium Pharmaceuticals, Inc.

Investigators

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

Study Documents (Full-Text)

• Statistical Analysis Plan - Dec 2, 2019
• Study Protocol - Sep 24, 2019

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.: Drug Therapy
• Additional relevant MeSH terms: Rifampin

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 1 investigative site in the United States from 15 October 2019 to 16 November 2019.
Pre-assignment Detail	Healthy 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 Title	Sequence AB: TAK-906 25 mg + TAK-906 25 mg and Rifampin 600 mg	Sequence BA: TAK-906 25 mg and Rifampin 600 mg + TAK-906 25 mg
Arm/Group Description	TAK-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)
STARTED	6	6
COMPLETED	6	6
NOT COMPLETED	0	0
Period Title: Study Period 1 (1 Day)
STARTED	6	6
COMPLETED	6	6
NOT COMPLETED	0	0
Period Title: Study Period 1 (1 Day)
STARTED	6	6
COMPLETED	6	6
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Sequence AB: TAK-906 25 mg + TAK-906 25 mg and Rifampin 600 mg	Sequence BA: TAK-906 25 mg and Rifampin 600 mg + TAK-906 25 mg	Total
Arm/Group Description	TAK-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 Participants	6	6	12
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

Title	Cmax: Maximum Observed Plasma Concentration for TAK-906
Time Frame	Day 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 Title	Treatment A: TAK-906 25 mg	Treatment B: Rifampin 600 mg and TAK-906 25 mg
Arm/Group Description	TAK-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 Participants	12	12
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 Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	6.24
	Confidence Interval	(2-Sided) 90%; 4.62 to 8.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-906
Time Frame	Day 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 Title	Treatment A: TAK-906 25 mg	Treatment B: Rifampin 600 mg and TAK-906 25 mg
Arm/Group Description	TAK-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 Participants	12	12
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 Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	5.16
	Confidence Interval	(2-Sided) 90%; 4.25 to 6.25
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	AUClast: Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-906
Time Frame	Day 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 Title	Treatment A: TAK-906 25 mg	Treatment B: Rifampin 600 mg and TAK-906 25 mg
Arm/Group Description	TAK-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 Participants	12	12
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 Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	5.21
	Confidence Interval	(2-Sided) 90%; 4.29 to 6.32
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Participants Reporting One or More Treatment-emergent Adverse Events (TEAEs)
Time Frame	Baseline 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 Title	Treatment A: TAK-906 25 mg	Treatment B: Rifampin 600 mg and TAK-906 25 mg
Arm/Group Description	TAK-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 Participants	12	12
Count of Participants [Participants]	6 100%	2 33.3%

5. Secondary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Vital Sign Values
Time Frame	Baseline 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 Title	Treatment A: TAK-906 25 mg	Treatment B: Rifampin 600 mg and TAK-906 25 mg
Arm/Group Description	TAK-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 Participants	12	12
Count of Participants [Participants]	0 0%	0 0%

6. Secondary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in 12-lead Electrocardiogram (ECG) Findings
Time Frame	Baseline 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 Title	Treatment A: TAK-906 25 mg	Treatment B: Rifampin 600 mg and TAK-906 25 mg
Arm/Group Description	TAK-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 Participants	12	12
Count of Participants [Participants]	0 0%	0 0%

7. Secondary Outcome

Title	Number of Participants With Clinically Significant Change From Baseline in Clinical Laboratory Values
Time Frame	Baseline 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 Title	Treatment A: TAK-906 25 mg	Treatment B: Rifampin 600 mg and TAK-906 25 mg
Arm/Group Description	TAK-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 Participants	12	12
Count of Participants [Participants]	0 0%	0 0%

Adverse Events

Time Frame	TEAEs 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 Title	Treatment A: TAK-906 25 mg		Treatment B: Rifampin 600 mg and TAK-906 25 mg
Arm/Group Description	TAK-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 mg		Treatment B: Rifampin 600 mg and TAK-906 25 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Serious Adverse Events
	Treatment A: TAK-906 25 mg		Treatment B: Rifampin 600 mg and TAK-906 25 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Treatment A: TAK-906 25 mg		Treatment B: Rifampin 600 mg and TAK-906 25 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/12 (50%)		2/12 (16.7%)
Gastrointestinal disorders
Abdominal pain upper	1/12 (8.3%)		0/12 (0%)
Nervous system disorders
Headache	2/12 (16.7%)		1/12 (8.3%)
Sensory disturbance	1/12 (8.3%)		0/12 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/12 (0%)		1/12 (8.3%)
Nasal congestion	0/12 (0%)		1/12 (8.3%)
Sinus congestion	1/12 (8.3%)		0/12 (0%)
Sneezing	1/12 (8.3%)		0/12 (0%)
Skin and subcutaneous tissue disorders
Dermatitis contact	1/12 (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.