A Drug Interaction Study of KW-6356 With Midazolam, Caffeine, or Rosuvastatin

Phase 1

Completed

• Conditions: Parkinson's Disease
• Interventions: Drug: Midazolam; Drug: Caffeine; Drug: Rosuvastatin; Drug: KW-6356

• Registration Number: NCT03970798
• Lead Sponsor: Kyowa Kirin Co., Ltd.

Brief Summary

The purpose of this study is to evaluate the influence of repeated oral doses of KW-6356 on the pharmacokinetics of index substrates for CYP3A4/5, CYP1A2 and BCRP.

Detailed Description

Not available

Study Timeline

• Study Start: 2019-05-22
• Study First Submitted: 2019-05-23
• Study First Submitted QC: 2019-05-30
• Study First Posted: 2019-06-03
• Primary Completion: 2019-07-31
• Study Completion: 2019-07-31
• Status Verified: 2019-11
• Last Update Submitted: 2019-11-27
• Last Update Posted: 2019-11-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 50

Inclusion Criteria

1. Individuals having issued written consent to this study at their own discretion
2. Japanese males aged 20 to 44 years at the time of informed consent
3. Body mass index (BMI) of 18.5 to <25.0 at screening
4. Resting pulse rate of 40 to 100 bpm, systolic blood pressure of 90 to 139 mmHg, and diastolic blood pressure of 40 to 89 mmHg when measured in the supine position at screening

Exclusion Criteria

1. Individuals with any current disease requiring treatment
2. Individuals having drug allergy or its history
3. Individuals having psychiatric disease or its history
4. Positive results for any of the following infection-related items examined at screening: hepatitis B surface (HBs) antigen, HBs antibody, hepatitis B core (HBc) antibody, hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antigen/antibody, human T-lymphotropic virus (HTLV)-1 antibody, rapid plasma reagin (PRP) test, Treponema pallidum (TP) antibody.
5. Individuals with clinically significant abnormality detected on 12-lead electrocardiogram (ECG) recorded prior to the first dose of index substrate.
6. Individuals categorized as patients listed in the warnings or contraindications section of the package insert of any of the relevant index substrates (see separate protocol annex 6-8)
7. Individuals having used any drug (including over-the-counter [OTC] drugs, topical agents, vitamin preparations, health supplements, and Chinese herbal medicines) within 2 weeks prior to the first dose of index substrate.
8. Individuals having consumed grapefruit (including any food or beverage containing grapefruit) or any food or beverage containing St John's wort within 1 week prior to the first dose of index substrate.
9. Individuals having smoked or used smoking cessation agents (including chewing or eating of nicotine-containing products and application of nicotine patches) within 4 weeks prior to the first dose of index substrate.
10. Individuals having received inpatient treatment or surgery within 12 weeks prior to the first dose of index substrate.
11. Individuals having participated in a clinical study of a pharmaceutical product or a medical device or any equivalent study and used the investigational product or the unapproved medical device within 16 weeks prior to the first dose of index substrate.
12. Individuals having undergone collection of ≥400 mL of blood within 12 weeks prior to the first dose of index substrate or ≥200 mL of blood within 4 weeks prior to the first dose of index substrate (for blood donation or clinical trial, etc.) or pheresis donation (plateletpheresis or plasmapheresis donation) within 2 weeks prior to the first dose of index substrate.
13. Individuals having issued no consent to adoption of any appropriate contraceptive method during a period from day of admission to 12 weeks after the final dose of the study drug. The appropriate contraceptive method is defined as sexual abstinence or use of 2 of the following contraceptive devices: condom, oral contraceptives, intrauterine device, and pessary.
14. Individuals having received KW-6356 before.
15. Other individuals unsuitable for participating in the study in the opinion of the investigator or subinvestigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
KW-6356/Healthy Japanese adult male subjects	Midazolam	Period 1: intake of the index substrates at Day 1 (Cohort 1: midazolam, Cohort 2: caffeine + rosuvastatin) followed by Period 2: intake of KW-6356 at Day 4-13, intake of the index substrates at Day 11
KW-6356/Healthy Japanese adult male subjects	Caffeine	Period 1: intake of the index substrates at Day 1 (Cohort 1: midazolam, Cohort 2: caffeine + rosuvastatin) followed by Period 2: intake of KW-6356 at Day 4-13, intake of the index substrates at Day 11
KW-6356/Healthy Japanese adult male subjects	Rosuvastatin	Period 1: intake of the index substrates at Day 1 (Cohort 1: midazolam, Cohort 2: caffeine + rosuvastatin) followed by Period 2: intake of KW-6356 at Day 4-13, intake of the index substrates at Day 11
KW-6356/Healthy Japanese adult male subjects	KW-6356	Period 1: intake of the index substrates at Day 1 (Cohort 1: midazolam, Cohort 2: caffeine + rosuvastatin) followed by Period 2: intake of KW-6356 at Day 4-13, intake of the index substrates at Day 11

Primary Outcome Measures

Name	Time	Method
Geometric mean ratio of the major pharmacokinetic parameter (AUC0-t) of the index substrates in combination with or without KW-6356	Starting around 2 hours before intake of the index substrates and continued until 24 hours after the last dose of KW-6356

Secondary Outcome Measures

Name	Time	Method
Plasma concentrations of the index substrates	Starting around 2 hours before intake of the index substrates and continued until 24 hours after the last dose of KW-6356
Geometric mean ratio of the major pharmacokinetic parameters (Cmax) of the index substrates in combination with or without KW-6356	Starting around 2 hours before intake of the index substrates and continued until 24 hours after the last dose of KW-6356
Geometric mean ratio of the major pharmacokinetic parameters (AUC0-∞) of the index substrates in combination with or without KW-6356	Starting around 2 hours before intake of the index substrates and continued until 24 hours after the last dose of KW-6356
Pharmacokinetic parameters (tmax) of the index substrates	Starting around 2 hours before intake of the index substrates and continued until 24 hours after the last dose of KW-6356
Pharmacokinetic parameters (CL/F) of the index substrates	Starting around 2 hours before intake of the index substrates and continued until 24 hours after the last dose of KW-6356
Pharmacokinetic parameters (Vz/F) of the index substrates	Starting around 2 hours before intake of the index substrates and continued until 24 hours after the last dose of KW-6356
Pharmacokinetic parameters (t1/2) of the index substrates	Starting around 2 hours before intake of the index substrates and continued until 24 hours after the last dose of KW-6356
Plasma concentrations of KW-6356	Starting around 2 hours before intake of KW-6356 and continued until 24 hours after the last dose of KW-6356
Incidence of treatment-emergent adverse events	Starting 24 or 48 hours before intake of the index substrates and continued until 8 days after the last dose of KW-6356

Trial Locations

Locations (1)

Fukuoka Mirai Hospital Clinical Research Center; 🇯🇵 Fukuoka, Japan