A Study to Evaluate the Effect of Food on the Pharmacokinetics of TAK-831 Tablet Formulation

Sponsor

Neurocrine Biosciences (Industry)

Overall Status

Completed

CT.gov ID

NCT03101293

Collaborator

Takeda (Industry)

Enrollment

Location

Arms

1.7

Actual Duration (Months)

8.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the pharmacokinetic (PK) of a single oral dose of TAK-831 400 milligram (mg) in the fasted state and to estimate the effect of food on the PK of a single oral dose of TAK-831 400 mg when administered as tablet formulation in healthy participants.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: TAK-831	Phase 1

Detailed Description

The drug being tested in this study is called TAK-831. TAK-831 is being tested in healthy participants under fasting and fed conditions in order to determine the effect of food on the PK of single oral dose of TAK-831 tablet formulation. The study will enroll approximately 16 participants. Participants will be randomly and equally assigned (by chance, like flipping a coin) to 1 of the 2 treatment sequences following as:

TAK-831 400 mg Fasted + TAK-831 400 mg Fed
TAK-831 400 mg Fed + TAK-831 400 mg Fasted All participants will be asked to take single oral dose of TAK-831 tablet at the same time on Day 1 of each Intervention Period. This single center trial will be conducted in the United States. The overall time to participate in this study is 23 days. Participants will visit the clinic on Day -1 and remained confined until Day 3 of Intervention Period 1 and 2. A washout period of minimum 7 days will be maintained between the doses in each Intervention Period. Participants will make 3 visits to the clinic on Days 4, 6 and 8 on each Intervention Period and will be contacted by telephone 14 days after the last dose of study drug (Day

for a follow-up assessment.

Study Design

Study Type:

Interventional

Actual Enrollment :

15 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

A Randomized, Open-Label, Single-Dose, 2-Period, Crossover Design, Phase 1 Study to Evaluate the Effect of Food on the Pharmacokinetics of TAK-831 T2 Tablet Formulation in Healthy Subjects

Actual Study Start Date :

Apr 4, 2017

Actual Primary Completion Date :

May 19, 2017

Actual Study Completion Date :

May 26, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TAK-831 400 mg Fasted + TAK-831 400 mg Fed TAK-831 400 mg, film-coated tablets, orally under fasted state, once on Day 1 of Intervention Period 1, followed by 7 days washout period, further followed by TAK-831 400 mg, film-coated tablets, orally under fed state, once on Day 1 of Intervention Period 2.	Drug: TAK-831 TAK-831 film-coated tablet.
Experimental: TAK-831 400 mg Fed + TAK-831 400 mg Fasted TAK-831 400 mg, film-coated tablets, orally under fed state, once on Day 1 of Intervention Period 1, followed by 7 days washout period, further followed by TAK-831 400 mg, film-coated tablets, orally under fasted state, once on Day 1 of Intervention Period 2.	Drug: TAK-831 TAK-831 film-coated tablet.

Arm

Intervention/Treatment

Experimental: TAK-831 400 mg Fasted + TAK-831 400 mg Fed

TAK-831 400 mg, film-coated tablets, orally under fasted state, once on Day 1 of Intervention Period 1, followed by 7 days washout period, further followed by TAK-831 400 mg, film-coated tablets, orally under fed state, once on Day 1 of Intervention Period 2.

Drug: TAK-831

TAK-831 film-coated tablet.

Experimental: TAK-831 400 mg Fed + TAK-831 400 mg Fasted

TAK-831 400 mg, film-coated tablets, orally under fed state, once on Day 1 of Intervention Period 1, followed by 7 days washout period, further followed by TAK-831 400 mg, film-coated tablets, orally under fasted state, once on Day 1 of Intervention Period 2.

Drug: TAK-831

TAK-831 film-coated tablet.

Outcome Measures

Primary Outcome Measures

Cmax: Maximum Observed Plasma Concentration for TAK-831 [Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose]
AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831 [Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose]
AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831 [Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose]

Secondary Outcome Measures

Percentage of Participants Who Experience at Least 1 Treatment-emergent Adverse Event (TEAE) [Day 1]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Weighs greater than or equal to (>=) 45 kilogram (kg) and has a body mass index (BMI) between 18.0 and 30.0 kilogram per square meter (kg/m^2), inclusive at Screening.

Exclusion Criteria:

Has received TAK-831 in a previous clinical study.
Has poor peripheral venous access.
Has donated or lost 450 milliliter (mL) or more of his or her blood volume (including plasmapheresis), or had a transfusion of any blood product within 45 days prior to first dose of study drug.
Has any dietary restrictions or preferences that may interfere with the conduct of the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	PRA Health Sciences	Lenexa	Kansas	United States	66219

Sponsors and Collaborators

Neurocrine Biosciences
Takeda

Investigators

None specified.

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

Neurocrine Biosciences

ClinicalTrials.gov Identifier:

NCT03101293

Other Study ID Numbers:

TAK-831-1004
U1111-1189-8001

First Posted:

Apr 5, 2017

Last Update Posted:

Jun 14, 2021

Last Verified:

Jun 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Neurocrine Biosciences

Drug therapy

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 1 investigative site in the United States from 04 April 2017 to 26 May 2017.
Pre-assignment Detail	Healthy participants were enrolled in this 2-way crossover study and randomized in 1 of the 2 treatment sequences which determined the order to receive TAK-831 400 milligram (mg) film-coated tablets under fasted conditions and TAK-831 400 mg tablet under fed conditions (nutritional drink).

Arm/Group Title	TAK-831 400 mg Fasted + TAK-831 400 mg Fed	TAK-831 400 mg Fed + TAK-831 400 mg Fasted
Arm/Group Description	TAK-831 400 mg, film-coated tablets, orally, under fasted state, once on Day 1 of Intervention Period 1, followed by at least 7 days of washout period, further followed by TAK-831 400 mg, tablet, orally, under fed state, once on Day 1 of Intervention Period 2.	TAK-831 400 mg, film-coated tablets, orally, under fed state, once on Day 1 of Intervention Period 1, followed by at least 7 days of washout period, further followed by TAK-831 400 mg, tablet, orally, under fasted state, once on Day 1 of Intervention Period 2.
Period Title: Intervention Period 1
STARTED	7	8
COMPLETED	7	8
NOT COMPLETED	0	0
Period Title: Intervention Period 1
STARTED	7	8
COMPLETED	6	8
NOT COMPLETED	1	0
Period Title: Intervention Period 1
STARTED	6	8
COMPLETED	6	8
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	TAK-831 400 mg Fasted + TAK-831 400 mg Fed	TAK-831 400 mg Fed + TAK-831 400 mg Fasted	Total
Arm/Group Description	TAK-831 400 mg, film-coated tablets, orally, under fasted state, once on Day 1 of Intervention Period 1, followed by at least 7 days of washout period, further followed by TAK-831 400 mg, tablet, orally, under fed state, once on Day 1 of Intervention Period 2.	TAK-831 400 mg, film-coated tablets, orally, under fed state, once on Day 1 of Intervention Period 1, followed by at least 7 days of washout period, further followed by TAK-831 400 mg, tablet, orally, under fasted state, once on Day 1 of Intervention Period 2.	Total of all reporting groups
Overall Participants	7	8	15
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	35.4 (7.98)	32.6 (11.22)	33.9 (9.61)
Sex: Female, Male (Count of Participants)
Female	1 14.3%	2 25%	3 20%
Male	6 85.7%	6 75%	12 80%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 14.3%	0 0%	1 6.7%
Not Hispanic or Latino	6 85.7%	8 100%	14 93.3%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 14.3%	0 0%	1 6.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	3 42.9%	3 37.5%	6 40%
White	3 42.9%	5 62.5%	8 53.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	7 100%	8 100%	15 100%
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	73.3 (9.65)	78.6 (11.19)	76.1 (10.48)
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	171.3 (6.40)	173.8 (7.19)	172.6 (6.71)
Body Mass Index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]	24.9 (2.17)	25.9 (2.45)	25.5 (2.30)
Smoking Classification (Count of Participants)
Never smoked	5 71.4%	7 87.5%	12 80%
Current smoker	1 14.3%	0 0%	1 6.7%
Ex-smoker	1 14.3%	1 12.5%	2 13.3%
Alcohol Classification (Count of Participants)
Never drunk	3 42.9%	3 37.5%	6 40%
Current drinker	4 57.1%	5 62.5%	9 60%
Ex-drinker	0 0%	0 0%	0 0%
Caffeine Consumption (Count of Participants)
Caffeine consumption	6 85.7%	7 87.5%	13 86.7%
No caffeine consumption	1 14.3%	1 12.5%	2 13.3%
Xanthine Consumption (Count of Participants)
Xanthine consumption	6 85.7%	7 87.5%	13 86.7%
No xanthine consumption	1 14.3%	1 12.5%	2 13.3%
Female Reproductive Status (Count of Participants)
Post-menopausal	0 0%	1 12.5%	1 6.7%
Surgically sterile	1 14.3%	1 12.5%	2 13.3%
Not applicable (Male)	6 85.7%	6 75%	12 80%

Outcome Measures

1. Primary Outcome

Title	Cmax: Maximum Observed Plasma Concentration for TAK-831
Description
Time Frame	Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose

Outcome Measure Data

Analysis Population Description
The pharmacokinetic (PK) analysis set included all participants from the safety set who had at least 1 measurable postdose TAK-831 plasma concentration.

Arm/Group Title	TAK-831 400 mg Fasted	TAK-831 400 mg Fed
Arm/Group Description	TAK-831 400 mg, film-coated tablets, orally, under fasted state, once on Day 1 of either Intervention Period 1 or Intervention Period 2.	TAK-831 400 mg, film-coated tablets, orally, under fed state, once on Day 1 of Intervention Period 1 or Intervention Period 2.
Measure Participants	15	14
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)]	650.04 (47.7)	865.48 (53.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAK-831 400 mg Fasted, TAK-831 400 mg Fed
	Comments
	Type of Statistical Test	Equivalence
	Comments	A linear mixed effect model on the natural log-transformed parameters was performed with regimen, sequence and period as fixed effects and participant nested within sequence as a random effect. The least squares means and difference of least squares means for the log-transformed parameters were exponentiated to obtain the point estimates of the food effect and 90% confidence intervals (CIs).

Statistical Test of Hypothesis	p-Value	0.0058
	Comments
	Method	ANOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	1.343
	Confidence Interval	(2-Sided) 90% 1.146 to 1.574
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831
Description
Time Frame	Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose

Outcome Measure Data

Analysis Population Description
The PK analysis set included all participants from the safety set who had at least 1 measurable postdose TAK-831 plasma concentration.

Arm/Group Title	TAK-831 400 mg Fasted	TAK-831 400 mg Fed
Arm/Group Description	TAK-831 400 mg, film-coated tablets, orally, under fasted state, once on Day 1 of either Intervention Period 1 or Intervention Period 2.	TAK-831 400 mg, film-coated tablets, orally, under fed state, once on Day 1 of Intervention Period 1 or Intervention Period 2.
Measure Participants	15	14
Geometric Mean (Geometric Coefficient of Variation) [hournanogram per milliliter (hng/mL)]	2290.8 (53.1)	2535.6 (58.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAK-831 400 mg Fasted, TAK-831 400 mg Fed
	Comments
	Type of Statistical Test	Equivalence
	Comments	A linear mixed effect model on the natural log-transformed parameters was performed with regimen, sequence and period as fixed effects and participant nested within sequence as a random effect. The least squares means and difference of least squares means for the log-transformed parameters were exponentiated to obtain the point estimates of the food effect and 90% CIs.

Statistical Test of Hypothesis	p-Value	0.1763
	Comments
	Method	ANOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	1.121
	Confidence Interval	(2-Sided) 90% 0.969 to 1.298
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831
Description
Time Frame	Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose

Outcome Measure Data

Analysis Population Description
The PK analysis set included all participants from the safety set who had at least 1 measurable postdose TAK-831 plasma concentration. The PK analysis population where data at specified time points were available.

Arm/Group Title	TAK-831 400 mg Fasted	TAK-831 400 mg Fed
Arm/Group Description	TAK-831 400 mg, film-coated tablets, orally, under fasted state, once on Day 1 of either Intervention Period 1 or Intervention Period 2.	TAK-831 400 mg, film-coated tablets, orally, under fed state, once on Day 1 of Intervention Period 1 or Intervention Period 2.
Measure Participants	13	10
Geometric Mean (Geometric Coefficient of Variation) [h*ng/mL]	2194.8 (53.1)	2465.9 (67.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	TAK-831 400 mg Fasted, TAK-831 400 mg Fed
	Comments
	Type of Statistical Test	Equivalence
	Comments	A linear mixed effect model on the natural log-transformed parameters was performed with regimen, sequence and period as fixed effects and participant nested within sequence as a random effect. The least squares means and difference of least squares means for the log-transformed parameters were exponentiated to obtain the point estimates of the food effect and 90% CIs.

Statistical Test of Hypothesis	p-Value	0.2745
	Comments
	Method	ANOVA
	Comments

Method of Estimation	Estimation Parameter	LS Mean Ratio
	Estimated Value	1.154
	Confidence Interval	(2-Sided) 90% 0.929 to 1.433
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants Who Experience at Least 1 Treatment-emergent Adverse Event (TEAE)
Description
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description
The safety analysis set included all participants who were randomized and received at least 1 dose of study drug.

Arm/Group Title	TAK-831 400 mg Fasted	TAK-831 400 mg Fed
Arm/Group Description	TAK-831 400 mg, film-coated tablets, orally, under fasted state, once on Day 1 of either Intervention Period 1 or Intervention Period 2.	TAK-831 400 mg, film-coated tablets, orally, under fed state, once on Day 1 of Intervention Period 1 or Intervention Period 2.
Measure Participants	15	14
Number [percentage of participants]	0 0%	7.1 88.8%

Adverse Events

	TAK-831 400 mg Fasted		TAK-831 400 mg Fed
Time Frame	Treatment-emergent adverse events are adverse events that started after the first dose of study drug and no more than 14 days after the last dose of study drug (up to Day 23)
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-831 400 mg Fasted		TAK-831 400 mg Fed
Arm/Group Description	TAK-831 400 mg, film-coated tablets, orally, under fasted state, once on Day 1 of either Intervention Period 1 or Intervention Period 2.		TAK-831 400 mg, film-coated tablets, orally, under fed state, once on Day 1 of Intervention Period 1 or Intervention Period 2.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/14 (0%)
Serious Adverse Events
	TAK-831 400 mg Fasted		TAK-831 400 mg Fed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	TAK-831 400 mg Fasted		TAK-831 400 mg Fed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/15 (0%)		1/14 (7.1%)
Infections and infestations
Upper respiratory tract infection	0/15 (0%)	0	1/14 (7.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Generally, the PI may publish results of the study following the publication of results by the Sponsor.

Results Point of Contact

Name/Title	Neurocrine Medical Information
Organization	Neurocrine Biosciences
Phone	877-641-3461
Email	medinfo@neurocrine.com

Responsible Party:

Neurocrine Biosciences

ClinicalTrials.gov Identifier:

NCT03101293

Other Study ID Numbers:

TAK-831-1004
U1111-1189-8001

First Posted:

Apr 5, 2017

Last Update Posted:

Jun 14, 2021

Last Verified:

Jun 1, 2021

A Study to Evaluate the Effect of Food on the Pharmacokinetics of TAK-831 Tablet Formulation

Study Details

Study Description

Brief Summary

Detailed Description

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact