Drug-Drug Interaction Study: ASP2151 and Bupropion

A Single-centre, Open-label Study in Healthy Men to Investigate the Effect of Repeated Oral Doses of ASP2151 on the Pharmacokinetics of Bupropion

CYP2B6 is involved in the metabolism of many drugs. So, it is important to assess in vivo the effect of ASP2151 on that enzyme to determine any possible drug interactions. The aim of this trial is to investigate the potential for interaction of ASP2151 with the CYP2B6 probe substrate bupropion.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Bupropion; Drug: ASP2151

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, NW10 7EW
    • Hammersmith Medicines Research Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• A body mass index (Quetelet index) in the range 18.0-30.9.
• Sufficient intelligence to understand the nature of the trial and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial.
• Willingness to give written consent to participate after reading the information and consent form, and after having the opportunity to discuss the trial with the investigator or his delegate.
• Willingness to give written consent to have data entered into The Overvolunteering Prevention System.

Exclusion Criteria:

• Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the volunteer.
• Any of the following liver function tests higher than 1.5 times the ULN at the screening visit: aspartate aminotransferase (AST), alanine aminotransferase (ALT), ALP, bilirubin, gamma glutamyl transpeptidase (gamma-GT).
• Platelet counts outside normal limits (129,000-346,000/μL).
• Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the volunteer's participation in the trial or make it unnecessarily hazardous.
• Clinically significant impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease, or history of any psychotic mental illness.
• History of bleeding diathesis, head injury, intracranial mass lesions, hydrocephalus, epilepsy, seizures, depression, self-harm (or thoughts of self-harm) or eating disorders.
• Surgery (eg stomach bypass) or medical condition that might affect absorption of medicines.
• Presence or history of severe adverse reaction to any drug, history of multiple drug allergies (multiple defined as >3), or sensitivity to trial medication.
• Use, during the 28 days before the first dose of trial medication, of any prescription medicine, or any other medicine or herbal remedy (such as St John's wort) known to interfere with the CYP3A4, CYP2C8, CYP2B6, CYP2D6 or CYP2C19 metabolic pathway.
• Use, during the 7 days before the first dose of trial medication, of any over-the-counter medicine, with the exception of paracetamol (acetaminophen).
• Participation in another clinical trial of a new chemical entity or a prescription medicine within the previous 3 months.
• Presence or history of drug or alcohol abuse, or intake of more than 21 units of alcohol weekly.
• Current smoker or history of regular use of tobacco or nicotine-containing products within the previous 6 months.
• Blood pressure and heart rate in seated position at the screening examination outside the ranges 90-140 mm Hg systolic, 40-90 mm Hg diastolic; heart rate 40_100 beats/min. However, if the investigator deems the result to be not clinically significant the subject may be included.
• Possibility that the volunteer will not cooperate with the requirements of the protocol.
• Evidence of drug abuse on urine testing.
• Positive test for hepatitis B, hepatitis C, HIV1 or HIV2.
• Loss of more than 400 mL blood during the 3 months before the trial, eg as a blood donor.
• Objection by General Practitioner (GP) to volunteer entering trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Bupropion + ASP2151; 400 mg ASP2151 followed by 150 mg Bupropion	Drug: Bupropion; Other Names: Zyban; Drug: ASP2151

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Peak Plasma Concentration (Cmax) of Bupropion	prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of Bupropion	prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serious and Non-Serious Adverse Events	Refer to the result of adverse event.	Up to 32 days after the last dose

Other Outcome Measures

Outcome Measure	Time Frame
Peak Plasma Concentration (Cmax) of Hydroxybupropion	prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
Time of Peak Concentration (Tmax) of Hydroxybupropion	prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of Hydroxybupropion	prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of Hydroxybupropion	prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
Half-life (t1/2) of Hydroxybupropion	prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
Trough Plasma Concentration (Ctrough) of ASP2151	Days 6-14 and at pre-dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15
Peak Plasma Concentration (Cmax) of ASP2151	prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15
Time of Peak Concentration (Tmax) of ASP2151	prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15
Area Under the Concentration-time Curve Over the Dosing Interval (AUC0-tau) of ASP2151	prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15
Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of ASP2151	prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15
Half-life (t1/2) of ASP2151	prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15
Apparent Volume of Distribution (Vd/F) of ASP2151	prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15
Apparent Total Body Clearance (CL/F) of ASP2151	prior to initial dose and 0.25, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 16 and 24 h after dosing on Day 15
Time of Peak Concentration (Tmax) of Bupropion	prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
Area Under the Curve Over up to Last No-zero Value (AUC0-tn) of Bupropion	prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
Half-life (t1/2) of Bupropion	prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
Apparent Volume of Distribution (Vd/F) of Bupropion	prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29
Apparent Total Body Clearance (CL/F) of Bupropion	prior to initial dose of Day 1 and 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 24, 36, 48, 60, 72 and 96 h after dosing on Day 1, Days 15, 22 and 29

Collaborators and Investigators

• Sponsor: Maruho Europe Limited

Study record dates

Study Major Dates

• Study Start: February 1, 2015
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: February 16, 2015
• First Submitted That Met QC Criteria: February 16, 2015
• First Posted (Estimate): February 23, 2015

Study Record Updates

• Last Update Posted (Actual): February 21, 2019
• Last Update Submitted That Met QC Criteria: January 31, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: volunteers; drug-drug interaction; Herpes
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Dopamine Uptake Inhibitors; Bupropion
• Other Study ID Numbers: M522101-EU25