A Phase I, Open-Label Trial to Assess the Absorption, Metabolism, and Excretion of (14C)-OPC-61815 in Healthy Male Japanese Subjects

• Sponsor: Otsuka Pharmaceutical Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04182958
• Collaborator: (none)
• Enrollment: 8
• Location: 1
• Arm: 1
• Actual Duration (Days): 24
• Patients Per Site Per Month: 10.1

Study Details

Study Description

Brief Summary

• To determine the mass balance of totalradioactivity following a single IV infusionof (14C)-OPC-61815.

• To determine routes and rates of elimination of total radioactivity following a single IV infusion of (14C)-OPC-61815

• To assess the PK of total radioactivity in plasma and whole blood following a single IV infusion of (14C)-OPC-61815

• To assess the PK of OPC-61815 free form and OPC-41061 in plasma following a single IV infusion of (14C)-OPC-61815

Condition or Disease	Intervention/Treatment	Phase
Healthy Adult Male	Drug: (14C)-OPC-61815	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I, Open-Label Trial to Assess the Mass Balance and Pharmacokinetics of a Single Intravenous Administration of (14C)-OPC-61815 to Healthy Male Japanese Subjects
• Actual Study Start Date: Nov 25, 2019
• Actual Primary Completion Date: Dec 19, 2019
• Actual Study Completion Date: Dec 19, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: (14C)-OPC-61815	Drug: (14C)-OPC-61815; On the morning of Day 1, all subjects will receive a single IV infusion of (14C) OPC-61815

Outcome Measures

Primary Outcome Measures

1. Area Under the Concentration-time Curve From Time Zero to Infinity (AUC∞) - Plasma OPC-61815 Free Form [48 hours after dose]

2. Maximum Peak Concentration (Cmax) - Plasma OPC-61815 Free Form [48 hours after dose]

3. Terminal-phase Elimination Half-life (t1/2,z) - Plasma OPC-61815 Free Form [48 hours after dose]

4. AUC∞ - Plasma OPC-41061 [48 hours after dose]

5. Cmax - Plasma OPC-41061 [48 hours after dose]

6. t1/2,z - Plasma OPC-41061 [48 hours after dose]

7. AUC∞ - Plasma Total Radioactivity [168 hours after dose]

8. Cmax - Plasma Total Radioactivity [168 hours after dose]

9. t1/2,z - Plasma Total Radioactivity [168 hours after dose]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 35 Years to 55 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male subjects between 35 and 55 years of age, inclusive; hold a valid Japanese passport and be first generation Japanese, defined as the subject, the subject's biological parent, and all of the subject's biological grandparents being of exclusive Japanese descent, have been born in Japan, and not lived outside of Japan for more than 5 years; with a body mass index between 18.5 and 28.0 kg/m2, inclusive, and a total body weight between 50 and 100 kg, inclusive; in good health, determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), vital sign measurements, and clinical laboratory evaluations at Screening and Check in as assessed by the investigator (or designee); and have a history of a minimum of 1 bowel movement per day.

Exclusion Criteria:

• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion; poor peripheral venous access; participation in a clinical trial involving administration of an investigational drug in the past 90 days prior to dosing; subjects with exposure to significant diagnostic or therapeutic radiation or current employment in a job requiring radiation exposure monitoring within 12 months prior to Check-in; subjects who have participated in any clinical trial involving a radiolabeled investigational drug within 12 months prior to Check-in.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Covance Clinical Research Unit Ltd	Leeds		United Kingdom	LS2 9LH

Sponsors and Collaborators

• Otsuka Pharmaceutical Co., Ltd.

Investigators

• Study Director: Takehisa Matsumaru, Mr, Otsuka Pharmaceutical Co., Ltd.

Study Documents (Full-Text)

• Study Protocol - Nov 14, 2019
• Statistical Analysis Plan - Dec 11, 2019

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Co., Ltd.
• ClinicalTrials.gov Identifier: NCT04182958
• Other Study ID Numbers: 263-102-00006; 2019-001968-29
• First Posted: Dec 2, 2019
• Last Update Posted: Oct 6, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Study Results

Participant Flow

Arm/Group Title	Overall: (14C)-OPC-61815
Arm/Group Description	Subjects were to receive a single IV infusion of 16 mg (14C)-OPC-61815, containing approximately 75.1 μCi (2.78 MBq), over a period of 60 minutes (55 to 65 minutes, inclusive) on Day 1 of the trial.
Period Title: Overall Study
STARTED	8
COMPLETED	8
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Overall: (14C)-OPC-61815
Arm/Group Description	Subjects were to receive a single IV infusion of 16 mg (14C)-OPC-61815, containing approximately 75.1 μCi (2.78 MBq), over a period of 60 minutes (55 to 65 minutes, inclusive) on Day 1 of the trial.
Overall Participants	8
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43 (5.8)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	8 100%
Race/Ethnicity, Customized (Count of Participants)
Japanese	8 100%
Region of Enrollment (Count of Participants)
United Kingdom	8 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Concentration-time Curve From Time Zero to Infinity (AUC∞) - Plasma OPC-61815 Free Form
Time Frame	48 hours after dose

Outcome Measure Data

Analysis Population Description

The PK population included all subjects that received (14C)-OPC-61815 (full dose within the time frame of 55 to 65 minutes, inclusive) and had evaluable PK data.

Arm/Group Title	Overall: (14C)-OPC-61815
Arm/Group Description	Subjects were to receive a single IV infusion of 16 mg (14C)-OPC-61815, containing approximately 75.1 μCi (2.78 MBq), over a period of 60 minutes (55 to 65 minutes, inclusive) on Day 1 of the trial.
Measure Participants	8
Mean (Standard Deviation) [h*ng/mL]	2060 (305)

2. Primary Outcome

Title	Maximum Peak Concentration (Cmax) - Plasma OPC-61815 Free Form
Time Frame	48 hours after dose

Outcome Measure Data

Analysis Population Description

The PK population included all subjects that received (14C)-OPC-61815 (full dose within the time frame of 55 to 65 minutes, inclusive) and had evaluable PK data.

Arm/Group Title	Overall: (14C)-OPC-61815
Arm/Group Description	Subjects were to receive a single IV infusion of 16 mg (14C)-OPC-61815, containing approximately 75.1 μCi (2.78 MBq), over a period of 60 minutes (55 to 65 minutes, inclusive) on Day 1 of the trial.
Measure Participants	8
Mean (Standard Deviation) [ng/mL]	1500 (156)

3. Primary Outcome

Title	Terminal-phase Elimination Half-life (t1/2,z) - Plasma OPC-61815 Free Form
Time Frame	48 hours after dose

Outcome Measure Data

Analysis Population Description

The PK population included all subjects that received (14C)-OPC-61815 (full dose within the time frame of 55 to 65 minutes, inclusive) and had evaluable PK data.

Arm/Group Title	Overall: (14C)-OPC-61815
Arm/Group Description	Subjects were to receive a single IV infusion of 16 mg (14C)-OPC-61815, containing approximately 75.1 μCi (2.78 MBq), over a period of 60 minutes (55 to 65 minutes, inclusive) on Day 1 of the trial.
Measure Participants	8
Mean (Standard Deviation) [hours]	3.61 (1.34)

4. Primary Outcome

Title	AUC∞ - Plasma OPC-41061
Time Frame	48 hours after dose

Outcome Measure Data

Analysis Population Description

The PK population included all subjects that received (14C)-OPC-61815 (full dose within the time frame of 55 to 65 minutes, inclusive) and had evaluable PK data.

Arm/Group Title	Overall: (14C)-OPC-61815
Arm/Group Description	Subjects were to receive a single IV infusion of 16 mg (14C)-OPC-61815, containing approximately 75.1 μCi (2.78 MBq), over a period of 60 minutes (55 to 65 minutes, inclusive) on Day 1 of the trial.
Measure Participants	8
Mean (Standard Deviation) [h*ng/mL]	1150 (230)

5. Primary Outcome

Title	Cmax - Plasma OPC-41061
Time Frame	48 hours after dose

Outcome Measure Data

Analysis Population Description

The PK population included all subjects that received (14C)-OPC-61815 (full dose within the time frame of 55 to 65 minutes, inclusive) and had evaluable PK data.

Arm/Group Title	Overall: (14C)-OPC-61815
Arm/Group Description	Subjects were to receive a single IV infusion of 16 mg (14C)-OPC-61815, containing approximately 75.1 μCi (2.78 MBq), over a period of 60 minutes (55 to 65 minutes, inclusive) on Day 1 of the trial.
Measure Participants	8
Mean (Standard Deviation) [ng/mL]	204 (27.9)

6. Primary Outcome

Title	t1/2,z - Plasma OPC-41061
Time Frame	48 hours after dose

Outcome Measure Data

Analysis Population Description

The PK population included all subjects that received (14C)-OPC-61815 (full dose within the time frame of 55 to 65 minutes, inclusive) and had evaluable PK data.

Arm/Group Title	Overall: (14C)-OPC-61815
Arm/Group Description	Subjects were to receive a single IV infusion of 16 mg (14C)-OPC-61815, containing approximately 75.1 μCi (2.78 MBq), over a period of 60 minutes (55 to 65 minutes, inclusive) on Day 1 of the trial.
Measure Participants	8
Mean (Standard Deviation) [hours]	5.27 (0.826)

7. Primary Outcome

Title	AUC∞ - Plasma Total Radioactivity
Time Frame	168 hours after dose

Outcome Measure Data

Analysis Population Description

The PK population included all subjects that received (14C)-OPC-61815 (full dose within the time frame of 55 to 65 minutes, inclusive) and had evaluable PK data.

Arm/Group Title	Overall: (14C)-OPC-61815
Arm/Group Description	Subjects were to receive a single IV infusion of 16 mg (14C)-OPC-61815, containing approximately 75.1 μCi (2.78 MBq), over a period of 60 minutes (55 to 65 minutes, inclusive) on Day 1 of the trial.
Measure Participants	8
Mean (Standard Deviation) [h*ngEq/mL]	30300 (4850)

8. Primary Outcome

Title	Cmax - Plasma Total Radioactivity
Time Frame	168 hours after dose

Outcome Measure Data

Analysis Population Description

The PK population included all subjects that received (14C)-OPC-61815 (full dose within the time frame of 55 to 65 minutes, inclusive) and had evaluable PK data.

Arm/Group Title	Overall: (14C)-OPC-61815
Arm/Group Description	Subjects were to receive a single IV infusion of 16 mg (14C)-OPC-61815, containing approximately 75.1 μCi (2.78 MBq), over a period of 60 minutes (55 to 65 minutes, inclusive) on Day 1 of the trial.
Measure Participants	8
Mean (Standard Deviation) [ngEq/mL]	2180 (188)

9. Primary Outcome

Title	t1/2,z - Plasma Total Radioactivity
Time Frame	168 hours after dose

Outcome Measure Data

Analysis Population Description

The PK population included all subjects that received (14C)-OPC-61815 (full dose within the time frame of 55 to 65 minutes, inclusive) and had evaluable PK data.

Arm/Group Title	Overall: (14C)-OPC-61815
Arm/Group Description	Subjects were to receive a single IV infusion of 16 mg (14C)-OPC-61815, containing approximately 75.1 μCi (2.78 MBq), over a period of 60 minutes (55 to 65 minutes, inclusive) on Day 1 of the trial.
Measure Participants	8
Mean (Standard Deviation) [hours]	128 (33.1)

Adverse Events

Time Frame	Treatment-emergent adverse events (TEAEs) were collected from the start of investigational medicinal product (IMP) administration up to 12 days
Adverse Event Reporting Description	The safety population included all subjects that received (14C)-OPC-61815.
Arm/Group Title	Overall: (14C)-OPC-61815
Arm/Group Description	Subjects were to receive a single IV infusion of 16 mg (14C)-OPC-61815, containing approximately 75.1 μCi (2.78 MBq), over a period of 60 minutes (55 to 65 minutes, inclusive) on Day 1 of the trial.
All Cause Mortality
	Overall: (14C)-OPC-61815
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Serious Adverse Events
	Overall: (14C)-OPC-61815
	Affected / at Risk (%)	# Events
Total	0/8 (0%)
Other (Not Including Serious) Adverse Events
	Overall: (14C)-OPC-61815
	Affected / at Risk (%)	# Events
Total	1/8 (12.5%)
Skin and subcutaneous tissue disorders
Rash	1/8 (12.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.