A Study to Evaluate the Relative Bioavailability (BA) and Effect of Food on TAK-831 Tablet Formulations in Healthy Participants

Sponsor
Neurocrine Biosciences (Industry)
Overall Status
Completed
CT.gov ID
NCT03706469
Collaborator
Takeda (Industry)
16
Enrollment
1
Location
4
Arms
2.1
Actual Duration (Months)
7.5
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the oral BA of TAK-831 T3 tablet formulation relative to TAK-831 T2 tablet formulation under fasting conditions and to assess the effect of food on the pharmacokinetics (PK) of TAK-831 T3 tablet formulation.

Condition or DiseaseIntervention/TreatmentPhase
  • Drug: TAK-831 T2
  • Drug: TAK-831 T3
Phase 1

Detailed Description

The drug being tested in this study is called TAK-831. TAK-831 is being tested in healthy participants to evaluate the relative BA and effect of food on the PK of TAK-831 tablet formulation.

The study will enroll approximately 16 participants. Participants will be randomly assigned (by chance, like flipping a coin) to TAK-831 in 1 of the 4 treatment sequences as following:

  • T2 50 mg Fasted + T3 50 mg Fasted + T3 600 mg Fasted + T2 600 mg Fasted + T3 600 mg Fed

  • T3 50 mg Fasted + T2 600 mg Fasted + T2 50 mg Fasted + T3 600 mg Fasted + T3 600 mg Fed

  • T2 600 mg Fasted + T3 600 mg Fasted + T3 50 mg Fasted + T2 50 mg Fasted + T3 600 mg Fed

  • T3 600 mg Fasted + T2 50 mg Fasted + T2 600 mg Fasted + T3 50 mg Fasted + T3 600 mg Fed

All participants will be asked to take tablet of assigned TAK-831 on Day 1 of each treatment period.

This single center trial will be conducted in the United States. The overall time to participate in this study is approximately 70 days. Participants will make multiple visits to the clinic and will be contacted by clinic approximately 14 days after the last dose of study drug for a follow-up assessment.

Study Design

Study Type:
Interventional
Actual Enrollment :
16 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Other
Official Title:
A Phase 1, Open-Label, Randomized, Single Dose, 5-Period, 5-Treatment Study to Evaluate the Relative Bioavailability and Effect of Food on TAK-831 Tablet Formulations in Healthy Subjects
Actual Study Start Date :
Oct 18, 2018
Actual Primary Completion Date :
Dec 11, 2018
Actual Study Completion Date :
Dec 22, 2018

Arms and Interventions

ArmIntervention/Treatment
Experimental: Fasted (T2 50 mg+T3 50 mg+T3 600 mg+T2 600 mg)+Fed (T3 600 mg)

TAK-831 T2 50 milligram (mg), tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, followed by TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 2, followed by TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 3, followed by TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 4, further followed by TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5. There will be a washout period of at least 7 days between study drug in-take in subsequent treatment periods.

Drug: TAK-831 T2
TAK-831 T2 Tablets.

Drug: TAK-831 T3
TAK-831 T3 Tablets.

Experimental: Fasted (T3 50 mg+T2 600 mg+T2 50 mg+T3 600 mg)+Fed (T3 600 mg)

TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, followed by TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 2, followed by TAK-831 T2 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 3, followed by TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 4, further followed by TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5. There will be a washout period of at least 7 days between study drug in-take in subsequent treatment periods.

Drug: TAK-831 T2
TAK-831 T2 Tablets.

Drug: TAK-831 T3
TAK-831 T3 Tablets.

Experimental: Fasted (T2 600 mg+T3 600 mg+T3 50 mg+T2 50 mg)+Fed (T3 600 mg)

TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, followed by TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 2, followed by TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 3, followed by TAK-831 T2 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 4, further followed by TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5. There will be a washout period of at least 7 days between study drug in-take in subsequent treatment periods.

Drug: TAK-831 T2
TAK-831 T2 Tablets.

Drug: TAK-831 T3
TAK-831 T3 Tablets.

Experimental: Fasted (T3 600 mg+T2 50 mg+T2 600 mg+T3 50 mg)+Fed (T3 600 mg)

TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, followed by TAK-831 T2 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 2, followed by TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 3, followed by TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 4, further followed by TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5. There will be a washout period of at least 7 days between study drug in-take in subsequent treatment periods.

Drug: TAK-831 T2
TAK-831 T2 Tablets.

Drug: TAK-831 T3
TAK-831 T3 Tablets.

Outcome Measures

Primary Outcome Measures

  1. 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]

  2. 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]

  3. Cmax: Maximum Observed Plasma Concentration for TAK-831 [Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose]

Secondary Outcome Measures

  1. Percentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE) [Day 1 post dose up to 14 days after the last dose of study drug (Up to Day 47)]

Eligibility Criteria

Criteria

Ages Eligible for Study:
19 Years to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
  1. Body mass index (BMI) greater than or equal to (>=) 18.0 and less than (<) 30.0 kilogram per square meter (kg/m^2), at Screening.
Exclusion Criteria:
  1. History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing.

  2. Smokes more than 20 cigarettes or equivalent per day within 3 months prior to the first dose and is unwilling to discontinue use of any tobacco- or nicotine-containing products during the confinement period(s) of the study.

  3. 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.

  4. Is lactose intolerant or unable/unwilling to eat the high-fat breakfast.

  5. Donation of blood or significant blood loss within 56 days prior to the first dosing.

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1CelerionLincolnNebraskaUnited States68502

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:
NCT03706469
Other Study ID Numbers:
  • TAK-831-1006
  • U1111-1217-5483
First Posted:
Oct 16, 2018
Last Update Posted:
Jun 14, 2021
Last Verified:
Jun 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Neurocrine Biosciences

Study Results

Participant Flow

Recruitment DetailsParticipants took part in the study at 1 investigative site in the United States from 18 October 2018 to 22 December 2018.
Pre-assignment DetailHealthy participants were enrolled and randomized in one of the 4 treatment sequences to receive TAK-831.
Arm/Group TitleFasted (T2 50 mg+T3 50 mg+T3 600 mg+T2 600 mg)+Fed (T3 600 mg)Fasted (T3 50 mg+T2 600 mg+T2 50 mg+T3 600 mg)+Fed (T3 600 mg)Fasted (T2 600 mg+T3 600 mg+T3 50 mg+T2 50 mg)+Fed (T3 600 mg)Fasted (T3 600 mg+T2 50 mg+T2 600 mg+T3 50 mg)+Fed (T3 600 mg)
Arm/Group DescriptionTAK-831 T2 50 milligram (mg), tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, followed by TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 2, followed by TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 3, followed by TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 4, further followed by TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5. There was a washout period of at least 7 days between study drug in-take in subsequent treatment periods.TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, followed by TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 2, followed by TAK-831 T2 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 3, followed by TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 4, further followed by TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5. There was a washout period of at least 7 days between study drug in-take in subsequent treatment periods.TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, followed by TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 2, followed by TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 3, followed by TAK-831 T2 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 4, further followed by TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5. There was a washout period of at least 7 days between study drug in-take in subsequent treatment periods.TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, followed by TAK-831 T2 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 2, followed by TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 3, followed by TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 4, further followed by TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5. There was a washout period of at least 7 days between study drug in-take in subsequent treatment periods.
Period Title: Overall Study
STARTED4444
COMPLETED4444
NOT COMPLETED0000

Baseline Characteristics

Arm/Group TitleFasted (T2 50 mg+T3 50 mg+T3 600 mg+T2 600 mg)+Fed (T3 600 mg)Fasted (T3 50 mg+T2 600 mg+T2 50 mg+T3 600 mg)+Fed (T3 600 mg)Fasted (T2 600 mg+T3 600 mg+T3 50 mg+T2 50 mg)+Fed (T3 600 mg)Fasted (T3 600 mg+T2 50 mg+T2 600 mg+T3 50 mg)+Fed (T3 600 mg)Total
Arm/Group DescriptionTAK-831 T2 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, followed by TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 2, followed by TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 3, followed by TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 4, further followed by TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5. There was a washout period of at least 7 days between study drug in-take in subsequent treatment periods.TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, followed by TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 2, followed by TAK-831 T2 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 3, followed by TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 4, further followed by TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5. There was a washout period of at least 7 days between study drug in-take in subsequent treatment periods.TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, followed by TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 2, followed by TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 3, followed by TAK-831 T2 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 4, further followed by TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5. There was a washout period of at least 7 days between study drug in-take in subsequent treatment periods.TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, followed by TAK-831 T2 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 2, followed by TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 3, followed by TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 4, further followed by TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5. There was a washout period of at least 7 days between study drug in-take in subsequent treatment periods.Total of all reporting groups
Overall Participants444416
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
40.3
(10.94)
49.0
(8.49)
31.8
(9.22)
30.0
(9.56)
37.8
(11.60)
Sex: Female, Male (Count of Participants)
Female
1
25%
4
100%
3
75%
2
50%
10
62.5%
Male
3
75%
0
0%
1
25%
2
50%
6
37.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
0
0%
0
0%
0
0%
0
0%
0
0%
Not Hispanic or Latino
4
100%
4
100%
4
100%
4
100%
16
100%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
0
0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
0
0%
0
0%
Asian
0
0%
0
0%
0
0%
0
0%
0
0%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
0
0%
0
0%
Black or African American
1
25%
0
0%
0
0%
0
0%
1
6.3%
White
3
75%
4
100%
4
100%
4
100%
15
93.8%
More than one race
0
0%
0
0%
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
0
0%
Region of Enrollment (Count of Participants)
United States
4
100%
4
100%
4
100%
4
100%
16
100%
Weight (kilogram (Kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (Kg)]
80.48
(9.694)
67.55
(6.815)
70.63
(19.643)
76.07
(4.666)
73.68
(11.660)
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]
175.3
(5.74)
168.3
(6.65)
169.5
(13.48)
169.3
(2.06)
170.6
(7.79)
Body mass index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]
26.060
(1.6219)
24.090
(4.1222)
24.250
(3.3966)
26.620
(1.9483)
25.255
(2.8796)

Outcome Measures

1. Primary Outcome
TitleAUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for TAK-831
Description
Time FrameDay 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 TitleTAK-831 T2 50 mg FastedTAK-831 T3 50 mg FastedTAK-831 T2 600 mg FastedTAK-831 T3 600 mg FastedTAK-831 T3 600 mg Fed
Arm/Group DescriptionTAK-831 T2 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5.
Measure Participants1616161616
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter(ng*hr/mL)]
714.8
(28.7)
597.5
(37.0)
4563
(24.8)
4665
(41.8)
8058
(29.0)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TAK-831 T2 50 mg Fasted, TAK-831 T3 50 mg Fasted
Comments
Type of Statistical Test Equivalence
Comments Bioequivalence in the AUClast will be concluded if the 90 percent (%) confidence interval for the test/reference ratio of the least squares means is fully contained within the acceptance range, 80.00% - 125.00%.
Statistical Test of Hypothesisp-Value
Comments
Method
Comments
Method of EstimationEstimation ParameterPercentage of Geometric Mean Ratio (GMR)
Estimated Value83.60
Confidence Interval (2-Sided) 90%
74.50 to 93.80
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TAK-831 T2 600 mg Fasted, TAK-831 T3 600 mg Fasted
Comments
Type of Statistical Test Equivalence
Comments Bioequivalence in the AUClast will be concluded if the 90% confidence interval for the test/reference ratio of the least squares means is fully contained within the acceptance range, 80.00% - 125.00%.
Statistical Test of Hypothesisp-Value
Comments
Method
Comments
Method of EstimationEstimation ParameterPercentage of GMR
Estimated Value102.22
Confidence Interval (2-Sided) 90%
91.10 to 114.70
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection TAK-831 T3 600 mg Fasted, TAK-831 T3 600 mg Fed
Comments
Type of Statistical Test Equivalence
Comments Bioequivalence in the AUClast will be concluded if the 90% confidence interval for the test/reference ratio of the least squares means is fully contained within the acceptance range, 80.00% - 125.00%.
Statistical Test of Hypothesisp-Value
Comments
Method
Comments
Method of EstimationEstimation ParameterPercentage of GMR
Estimated Value172.73
Confidence Interval (2-Sided) 90%
152.55 to 195.58
Parameter Dispersion Type:
Value:
Estimation Comments
2. Primary Outcome
TitleAUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for TAK-831
Description
Time FrameDay 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 TitleTAK-831 T2 50 mg FastedTAK-831 T3 50 mg FastedTAK-831 T2 600 mg FastedTAK-831 T3 600 mg FastedTAK-831 T3 600 mg Fed
Arm/Group DescriptionTAK-831 T2 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5.
Measure Participants1411161415
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]
761.8
(29.3)
688.6
(31.0)
4665
(26.0)
4558
(41.8)
7934
(27.3)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TAK-831 T2 50 mg Fasted, TAK-831 T3 50 mg Fasted
Comments
Type of Statistical Test Equivalence
Comments Bioequivalence in the AUC∞ will be concluded if the 90% confidence interval for the test/reference ratio of the least squares means is fully contained within the acceptance range, 80.00% - 125.00%.
Statistical Test of Hypothesisp-Value
Comments
Method
Comments
Method of EstimationEstimation ParameterPercentage of GMR
Estimated Value84.29
Confidence Interval (2-Sided) 90%
73.92 to 96.11
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TAK-831 T2 600 mg Fasted, TAK-831 T3 600 mg Fasted
Comments
Type of Statistical Test Equivalence
Comments Bioequivalence in the AUC∞ will be concluded if the 90% confidence interval for the test/reference ratio of the least squares means is fully contained within the acceptance range, 80.00% - 125.00%.
Statistical Test of Hypothesisp-Value
Comments
Method
Comments
Method of EstimationEstimation ParameterPercentage of GMR
Estimated Value99.61
Confidence Interval (2-Sided) 90%
88.88 to 111.63
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection TAK-831 T3 600 mg Fasted, TAK-831 T3 600 mg Fed
Comments
Type of Statistical Test Equivalence
Comments Bioequivalence in the AUC∞ will be concluded if the 90% confidence interval for the test/reference ratio of the least squares means is fully contained within the acceptance range, 80.00% - 125.00%.
Statistical Test of Hypothesisp-Value
Comments
Method
Comments
Method of EstimationEstimation ParameterPercentage of GMR
Estimated Value172.70
Confidence Interval (2-Sided) 90%
149.07 to 200.09
Parameter Dispersion Type:
Value:
Estimation Comments
3. Primary Outcome
TitleCmax: Maximum Observed Plasma Concentration for TAK-831
Description
Time FrameDay 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 TitleTAK-831 T2 50 mg FastedTAK-831 T3 50 mg FastedTAK-831 T2 600 mg FastedTAK-831 T3 600 mg FastedTAK-831 T3 600 mg Fed
Arm/Group DescriptionTAK-831 T2 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5.
Measure Participants1616161616
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)]
397.5
(38.8)
314.6
(40.0)
1384
(28.9)
1381
(24.6)
2394
(37.1)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TAK-831 T2 50 mg Fasted, TAK-831 T3 50 mg Fasted
Comments
Type of Statistical Test Equivalence
Comments Bioequivalence in the Cmax will be concluded if the 90% confidence interval for the test/reference ratio of the least squares means is fully contained within the acceptance range, 80.00% - 125.00%.
Statistical Test of Hypothesisp-Value
Comments
Method
Comments
Method of EstimationEstimation ParameterPercentage of GMR
Estimated Value79.14
Confidence Interval (2-Sided) 90%
67.36 to 92.99
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TAK-831 T2 600 mg Fasted, TAK-831 T3 600 mg Fasted
Comments
Type of Statistical Test Equivalence
Comments Bioequivalence in the Cmax will be concluded if the 90% confidence interval for the test/reference ratio of the least squares means is fully contained within the acceptance range, 80.00% - 125.00%.
Statistical Test of Hypothesisp-Value
Comments
Method
Comments
Method of EstimationEstimation ParameterPercentage of GMR
Estimated Value99.80
Confidence Interval (2-Sided) 90%
84.94 to 117.27
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection TAK-831 T3 600 mg Fasted, TAK-831 T3 600 mg Fed
Comments
Type of Statistical Test Equivalence
Comments Bioequivalence in the Cmax will be concluded if the 90% confidence interval for the test/reference ratio of the least squares means is fully contained within the acceptance range, 80.00% - 125.00%.
Statistical Test of Hypothesisp-Value
Comments
Method
Comments
Method of EstimationEstimation ParameterPercentage of GMR
Estimated Value173.30
Confidence Interval (2-Sided) 90%
150.05 to 200.16
Parameter Dispersion Type:
Value:
Estimation Comments
4. Secondary Outcome
TitlePercentage of Participants Who Experience at Least One Treatment Emergent Adverse Event (TEAE)
Description
Time FrameDay 1 post dose up to 14 days after the last dose of study drug (Up to Day 47)

Outcome Measure Data

Analysis Population Description
The safety analysis set included all participants who received at least one dose of the study drug(s).
Arm/Group TitleTAK-831 T2 50 mg FastedTAK-831 T3 50 mg FastedTAK-831 T2 600 mg FastedTAK-831 T3 600 mg FastedTAK-831 T3 600 mg Fed
Arm/Group DescriptionTAK-831 T2 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5.
Measure Participants1616161616
Number [percentage of participants]
0
0%
13
325%
0
0%
6
150%
0
0%

Adverse Events

Time FrameDay 1 post dose up to 14 days after the last dose of study drug ( Up to Day 47).
Adverse Event Reporting Description At each visit the investigator had to assess any occurrence of adverse events. Participants may report adverse events occurring at any other time during the study. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group TitleTAK-831 T2 50 mg FastedTAK-831 T3 50 mg FastedTAK-831 T2 600 mg FastedTAK-831 T3 600 mg FastedTAK-831 T3 600 mg Fed
Arm/Group DescriptionTAK-831 T2 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T3 50 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T2 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T3 600 mg, tablet, orally, once, under fasted condition on Day 1 of Treatment Period 1, 2, 3 or 4 as per assigned treatment sequence.TAK-831 T3 600 mg, tablet, orally, once, under fed condition on Day 1 of Treatment Period 5.
All Cause Mortality
TAK-831 T2 50 mg FastedTAK-831 T3 50 mg FastedTAK-831 T2 600 mg FastedTAK-831 T3 600 mg FastedTAK-831 T3 600 mg Fed
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/16 (0%) 0/16 (0%) 0/16 (0%) 0/16 (0%) 0/16 (0%)
Serious Adverse Events
TAK-831 T2 50 mg FastedTAK-831 T3 50 mg FastedTAK-831 T2 600 mg FastedTAK-831 T3 600 mg FastedTAK-831 T3 600 mg Fed
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/16 (0%) 0/16 (0%) 0/16 (0%) 0/16 (0%) 0/16 (0%)
Other (Not Including Serious) Adverse Events
TAK-831 T2 50 mg FastedTAK-831 T3 50 mg FastedTAK-831 T2 600 mg FastedTAK-831 T3 600 mg FastedTAK-831 T3 600 mg Fed
Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total0/16 (0%) 2/16 (12.5%) 0/16 (0%) 1/16 (6.3%) 0/16 (0%)
Gastrointestinal disorders
Constipation0/16 (0%) 1/16 (6.3%) 0/16 (0%) 0/16 (0%) 0/16 (0%)
Nervous system disorders
Headache0/16 (0%) 1/16 (6.3%) 0/16 (0%) 1/16 (6.3%) 0/16 (0%)

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/TitleNeurocrine Medical Information
OrganizationNeurocrine Biosciences
Phone877-641-3461
Emailmedinfo@neurocrine.com
Responsible Party:
Neurocrine Biosciences
ClinicalTrials.gov Identifier:
NCT03706469
Other Study ID Numbers:
  • TAK-831-1006
  • U1111-1217-5483
First Posted:
Oct 16, 2018
Last Update Posted:
Jun 14, 2021
Last Verified:
Jun 1, 2021