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

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.

Study Overview

• Status: Completed
• Conditions: Parkinson's Disease
• Intervention / Treatment: Drug: Midazolam; Drug: Caffeine; Drug: Rosuvastatin; Drug: KW-6356

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan
    • Fukuoka Mirai Hospital Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 44 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: KW-6356/Healthy Japanese adult male subjects; 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

Drug: Midazolam; In Period 1, Day 1 a single dose will be administered after fasting for at least 10 hours. In Period 2, Day 11 a single dose will be administered after fasting for at least 10 hours.; Drug: Caffeine; In Period 1, Day 1 a single dose will be administered after fasting for at least 10 hours. In Period 2, Day 11 a single dose will be administered after fasting for at least 10 hours.; Drug: Rosuvastatin; In Period 1, Day 1 a single dose will be administered after fasting for at least 10 hours. In Period 2, Day 11 a single dose will be administered after fasting for at least 10 hours.; Drug: KW-6356; In Period 2, Day 4-13(except Day11) a single dose of KW-6356 will be administered after breakfast, Day 11 a single dose of KW-6356 will be administered after fasting for at least 10 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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 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

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2019
• Primary Completion (Actual): July 31, 2019
• Study Completion (Actual): July 31, 2019

Study Registration Dates

• First Submitted: May 23, 2019
• First Submitted That Met QC Criteria: May 30, 2019
• First Posted (Actual): June 3, 2019

Study Record Updates

• Last Update Posted (Actual): November 29, 2019
• Last Update Submitted That Met QC Criteria: November 27, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Purinergic Antagonists; Purinergic Agents; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Phosphodiesterase Inhibitors; Purinergic P1 Receptor Antagonists; Central Nervous System Stimulants; Midazolam; Rosuvastatin Calcium; Caffeine
• Other Study ID Numbers: 6356-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No