A Study to Evaluate the Effect of High-Fat Meal on TAK-788 Pharmacokinetics (PK) in Healthy Adult Participants

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04441255
• Collaborator: (none)
• Enrollment: 14
• Location: 1
• Arms: 2
• Actual Duration (Months): 1.3
• Patients Per Site Per Month: 10.7

Study Details

Study Description

Brief Summary

The purpose of this study is to characterize the effect of a high-fat meal on the PK of TAK-788 administered in healthy participants.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Drug: TAK-788	Phase 1

Detailed Description

The drug being tested in this study is called TAK-788. The study will characterize the effect of a high-fat meal on the PK of TAK-788 administered in healthy participants.

The study will enroll approximately 14 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment sequence

• TAK-788 160 mg Fasted (Reference) in Period 1 + TAK-788 160 mg Fed (Test) in Period 2

• TAK-788 160 mg Fed (Test) in Period 1 + TAK-788 160 mg Fasted (Reference) in Period 2

All participants will be asked to take capsules of assigned TAK-788 on Day 1 of each period.

This single-center trial will be conducted in the United States. The overall time to participate in this study is 61 days. Participants will be contacted by telephone for 30 days after the last dose of study drug for a follow-up assessment.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Phase 1, Randomized, 2-Period, 2-Sequence, Crossover Study to Evaluate the Effect of High-Fat Meal on TAK-788 Pharmacokinetics in Healthy Adult Subjects
• Actual Study Start Date: Jul 1, 2020
• Actual Primary Completion Date: Aug 10, 2020
• Actual Study Completion Date: Aug 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TAK-788 160 mg Fasted + TAK-788 160 mg Fed TAK-788 160 milligram (mg), capsule, orally, once on Day 1 of Period 1 under fasted conditions (Treatment A), followed by 10 days washout period, followed by TAK-788 160 mg, capsule, orally, once on Day 1 of Period 2 under fed conditions (Treatment B).	Drug: TAK-788; TAK-788 Capsule.; Other Names: AP32788 Mobocertinib
Experimental: TAK-788 160 mg Fed + TAK-788 160 mg Fasted TAK-788 160 mg, capsule, orally, once on Day 1 of Period 1 under fed conditions (Treatment B), followed by 10 days washout period, followed by TAK-788 160 mg, capsule, orally, once on Day 1 of Period 2 under fasted conditions (Treatment A).	Drug: TAK-788; TAK-788 Capsule.; Other Names: AP32788 Mobocertinib

Outcome Measures

Primary Outcome Measures

1. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

2. Cmax: Maximum Observed Plasma Concentration for Mobocertinib [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

3. AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

4. AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Mobocertinib [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

Secondary Outcome Measures

1. Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Active Metabolites (AP32960 and AP32914) of Mobocertinib [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

2. Cmax: Maximum Observed Plasma Concentration for Active Metabolites (AP32960 and AP32914) of Mobocertinib [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

3. AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Active Metabolites (AP32960 and AP32914) of Mobocertinib [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

4. AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Active Metabolites (AP32960 and AP32914) of Mobocertinib [Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose]

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 20 years prior to the first dosing and throughout the study, based on participant self-reporting.

2. Body mass index (BMI) greater than or equal to (>=) 18.5 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 electrocardiogram (ECGs), as deemed by the Investigator or designee.

Exclusion Criteria:

1. History of any illness (including hyperlipidemia and diabetes since high fat meal is required) that, in the opinion of the Investigator or designee, might confound the results of the study or poses an additional risk to the participant by their participation in the study.

2. History or presence of alcoholism or drug abuse within the past 2 years prior to the first dosing.

3. History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds.

4. History or presence of any previous lung disease and/or current lung infection.

5. Positive urine drug or alcohol results at screening or first check-in.

6. Positive results at screening for Human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV).

7. Positive test result for active coronavirus disease 2019 (COVID-19).

8. Seated blood pressure is less than (<) 90/40 millimeter of mercury of mercury (mmHg) or greater than 140/90 mmHg at screening.

9. Seated heart rate is lower than 40 beats per minute (bpm) or higher than 99 bpm at screening.

10. QT interval corrected for heart rate using Fridericia's formula (QTcF) interval is greater than (>) 460 millisecond (msec) (males) or >470 msec (females) or ECG findings are deemed abnormal with clinical significance by the Investigator or designee at screening.

11. Creatinine clearance <90 milliliter per minute (mL/min) at screening (calculated using the Cockcroft-Gault formula).

12. Unable to refrain from or anticipates the use of:

o Any drug, including prescription and non-prescription medications, herbal remedies, or vitamin supplements within 14 days prior to the first dosing and throughout the study. Medication listed as part of acceptable birth control methods will be allowed. Thyroid hormone replacement medication may be permitted if the participant has been on the same stable dose for the immediate 3 months prior to the first dosing.

Acetaminophen (up to 2 gram per 24 hour period) may be permitted during the study, only after initial dosing, if necessary, to treat adverse events (AEs).

o Any drugs known to be inhibitors or inducers of Cytochrome P450 (CYP3A) enzymes and/or P-glycoprotein (P-gp), including St. John's Wort, within 28 days prior to the first dosing and throughout the study.

1. 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.

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

3. 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

• Takeda

Investigators

• Study Director: Study Director, Takeda

Study Documents (Full-Text)

• Study Protocol - Jun 9, 2020
• Statistical Analysis Plan - Aug 10, 2020

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT04441255
• Other Study ID Numbers: TAK-788-1005; CA24171
• First Posted: Jun 22, 2020
• Last Update Posted: Sep 5, 2021
• Last Verified: Aug 1, 2021

• 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 Takeda: Drug Therapy

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 1 investigative site in the United States from 01 July 2020 to 10 August 2020.
Pre-assignment Detail	Healthy participants were enrolled in 1 of the 2 treatment sequences of this 2-period cross-over study to receive mobocertinib (TAK-788) 160 milligram (mg), capsule, in fasted condition (Treatment A) or mobocertinib 160 mg, capsule, in fed condition (Treatment B).

Arm/Group Title	Mobocertinib 160 mg Fasted + Mobocertinib 160 mg Fed	Mobocertinib 160 mg Fed + Mobocertinib 160 mg Fasted
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once on Day 1 of Period 1 under fasted conditions (Treatment A), followed by 10 days washout period, further followed by mobocertinib 160 mg, capsule, orally, once on Day 1 of Period 2 under fed conditions (Treatment B).	Mobocertinib 160 mg, capsule, orally, once on Day 1 of Period 1 under fed conditions (Treatment B), followed by 10 days washout period, further followed by mobocertinib 160 mg, capsule, orally, once on Day 1 of Period 2 under fasted conditions (Treatment A).
Period Title: Period 1 (1 Day)
STARTED	7	7
COMPLETED	7	7
NOT COMPLETED	0	0
Period Title: Period 1 (1 Day)
STARTED	7	7
COMPLETED	7	7
NOT COMPLETED	0	0
Period Title: Period 1 (1 Day)
STARTED	7	7
COMPLETED	7	7
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Mobocertinib 160 mg Fasted + Mobocertinib 160 mg Fed	Mobocertinib 160 mg Fed + Mobocertinib 160 mg Fasted	Total
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once on Day 1 of Period 1 under fasted conditions (Treatment A), followed by 10 days washout period, further followed by mobocertinib 160 mg, capsule, orally, once on Day 1 of Period 2 under fed conditions (Treatment B).	Mobocertinib 160 mg, capsule, orally, once on Day 1 of Period 1 under fed conditions (Treatment B), followed by 10 days washout period, further followed by mobocertinib 160 mg, capsule, orally, once on Day 1 of Period 2 under fasted conditions (Treatment A).	Total of all reporting groups
Overall Participants	7	7	14
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.0 (9.61)	35.4 (9.14)	34.7 (9.04)
Sex: Female, Male (Count of Participants)
Female	2 28.6%	2 28.6%	4 28.6%
Male	5 71.4%	5 71.4%	10 71.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 14.3%	1 7.1%
Not Hispanic or Latino	7 100%	6 85.7%	13 92.9%
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 7.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 14.3%	2 28.6%	3 21.4%
White	5 71.4%	5 71.4%	10 71.4%
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%	7 100%	14 100%
Weight (kilogram (kg)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram (kg)]	73.89 (11.879)	76.70 (16.416)	75.29 (13.843)
Height (centimeter (cm)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [centimeter (cm)]	174.3 (9.48)	175.6 (13.50)	174.9 (11.23)
Body Mass Index (BMI) (kilogram per square meter (kg/m^2)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]	24.293 (3.0143)	24.706 (3.2743)	24.499 (3.0311)

Outcome Measures

1. Primary Outcome

Title	Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Mobocertinib
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The pharmacokinetic (PK) set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.

Arm/Group Title	Mobocertinib 160 mg Fasted	Mobocertinib 160 mg Fed
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once on Day 1 of either Period 1 or Period 2 under fasted conditions (Treatment A).	Mobocertinib 160 mg, capsule, orally, once on Day 1 of either Period 1 or Period 2 under fed conditions (Treatment B).
Measure Participants	13	14
Median (Full Range) [hours]	6.01	8.00

2. Primary Outcome

Title	Cmax: Maximum Observed Plasma Concentration for Mobocertinib
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.

Arm/Group Title	Mobocertinib 160 mg Fasted	Mobocertinib 160 mg Fed
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once on Day 1 of either Period 1 or Period 2 under fasted conditions (Treatment A).	Mobocertinib 160 mg, capsule, orally, once on Day 1 of either Period 1 or Period 2 under fed conditions (Treatment B).
Measure Participants	13	14
Geometric Mean (Geometric Coefficient of Variation) [nanogram per milliliter (ng/mL)]	56.8 (47.1)	56.6 (40.9)

3. Primary Outcome

Title	AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Mobocertinib
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.

Arm/Group Title	Mobocertinib 160 mg Fasted	Mobocertinib 160 mg Fed
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once on Day 1 of either Period 1 or Period 2 under fasted conditions (Treatment A).	Mobocertinib 160 mg, capsule, orally, once on Day 1 of either Period 1 or Period 2 under fed conditions (Treatment B).
Measure Participants	13	14
Geometric Mean (Geometric Coefficient of Variation) [nanogram*hour per milliliter (ng*hr/mL)]	1030 (61.1)	1230 (59.5)

4. Primary Outcome

Title	AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Mobocertinib
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.

Arm/Group Title	Mobocertinib 160 mg Fasted	Mobocertinib 160 mg Fed
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once on Day 1 of either Period 1 or Period 2 under fasted conditions (Treatment A).	Mobocertinib 160 mg, capsule, orally, once on Day 1 of either Period 1 or Period 2 under fed conditions (Treatment B).
Measure Participants	13	14
Geometric Mean (Geometric Coefficient of Variation) [ng*hr/mL]	1020 (61.4)	1210 (60.0)

5. Secondary Outcome

Title	Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Active Metabolites (AP32960 and AP32914) of Mobocertinib
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.

Arm/Group Title	Mobocertinib 160 mg Fasted	Mobocertinib 160 mg Fed
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once on Day 1 of either Period 1 or Period 2 under fasted conditions (Treatment A).	Mobocertinib 160 mg, capsule, orally, once on Day 1 of either Period 1 or Period 2 under fed conditions (Treatment B).
Measure Participants	13	14
AP32960	6.00	8.00
AP32914	6.01	8.00

6. Secondary Outcome

Title	Cmax: Maximum Observed Plasma Concentration for Active Metabolites (AP32960 and AP32914) of Mobocertinib
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.

Arm/Group Title	Mobocertinib 160 mg Fasted	Mobocertinib 160 mg Fed
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once on Day 1 of either Period 1 or Period 2 under fasted conditions (Treatment A).	Mobocertinib 160 mg, capsule, orally, once on Day 1 of either Period 1 or Period 2 under fed conditions (Treatment B).
Measure Participants	13	14
AP32960	31.1 (22.3)	27.7 (22.5)
AP32914	4.34 (31.7)	3.73 (31.8)

7. Secondary Outcome

Title	AUC∞: Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for Active Metabolites (AP32960 and AP32914) of Mobocertinib
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile. Here "number analyzed" were participants who were evaluable for the outcome measure at given categories.

Arm/Group Title	Mobocertinib 160 mg Fasted	Mobocertinib 160 mg Fed
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once on Day 1 of either Period 1 or Period 2 under fasted conditions (Treatment A).	Mobocertinib 160 mg, capsule, orally, once on Day 1 of either Period 1 or Period 2 under fed conditions (Treatment B).
Measure Participants	13	14
AP32960	704 (31.3)	731 (32.2)
AP32914	79.4 (47.4)	89.2 (50.6)

8. Secondary Outcome

Title	AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Active Metabolites (AP32960 and AP32914) of Mobocertinib
Time Frame	Day 1 pre-dose and at multiple time points (up to 240 hours) post-dose

Outcome Measure Data

Analysis Population Description

The PK set included all participants who complied sufficiently with the protocol and displayed an evaluable PK profile.

Arm/Group Title	Mobocertinib 160 mg Fasted	Mobocertinib 160 mg Fed
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once on Day 1 of either Period 1 or Period 2 under fasted conditions (Treatment A).	Mobocertinib 160 mg, capsule, orally, once on Day 1 of either Period 1 or Period 2 under fed conditions (Treatment B).
Measure Participants	13	14
AP32960	682 (31.9)	709 (32.7)
AP32914	69.2 (50.1)	72.2 (53.9)

Adverse Events

Time Frame	Treatment-emergent adverse events are adverse events that started after the first dose of study drug until 30 days after last dose of study drug in Period 2 (up to Day 42).
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	Mobocertinib 160 mg Fasted		Mobocertinib 160 mg Fed
Arm/Group Description	Mobocertinib 160 mg, capsule, orally, once on Day 1 of either Period 1 or Period 2 under fasted conditions (Treatment A).		Mobocertinib 160 mg, capsule, orally, once on Day 1 of either Period 1 or Period 2 under fed conditions (Treatment B).
All Cause Mortality
	Mobocertinib 160 mg Fasted		Mobocertinib 160 mg Fed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)
Serious Adverse Events
	Mobocertinib 160 mg Fasted		Mobocertinib 160 mg Fed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0%)		0/14 (0%)
Other (Not Including Serious) Adverse Events
	Mobocertinib 160 mg Fasted		Mobocertinib 160 mg Fed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/14 (35.7%)		6/14 (42.9%)
Gastrointestinal disorders
Abdominal pain upper	1/14 (7.1%)		1/14 (7.1%)
Diarrhoea	4/14 (28.6%)		3/14 (21.4%)
Gastrooesophageal reflux disease	0/14 (0%)		1/14 (7.1%)
Nausea	0/14 (0%)		2/14 (14.3%)
General disorders
Feeling abnormal	0/14 (0%)		1/14 (7.1%)
Feeling cold	1/14 (7.1%)		0/14 (0%)
Pain	1/14 (7.1%)		0/14 (0%)
Infections and infestations
Pustule	0/14 (0%)		1/14 (7.1%)
Injury, poisoning and procedural complications
Skin laceration	0/14 (0%)		1/14 (7.1%)
Musculoskeletal and connective tissue disorders
Muscle fatigue	0/14 (0%)		1/14 (7.1%)
Pain in extremity	1/14 (7.1%)		1/14 (7.1%)
Nervous system disorders
Dizziness	1/14 (7.1%)		0/14 (0%)
Headache	2/14 (14.3%)		2/14 (14.3%)
Respiratory, thoracic and mediastinal disorders
Pharyngeal erythema	0/14 (0%)		1/14 (7.1%)
Skin and subcutaneous tissue disorders
Erythema	0/14 (0%)		1/14 (7.1%)
Pruritus	0/14 (0%)		1/14 (7.1%)
Skin ulcer	0/14 (0%)		1/14 (7.1%)

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.