Clinical trial NCT02369172: Drug-Drug Interaction Study: ASP2151 and Bupropion
Official title: A Single-centre, Open-label Study in Healthy Men to Investigate the Effect of Repeated Oral Doses of ASP2151 on the Pharmacokinetics of Bupropion
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: Herpes
volunteers
drug-drug interaction
Lead sponsor: Maruho Europe Limited
Sponsor class: INDUSTRY
First posted: 2015-02-23
Enrollment: 24
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Peak Plasma Concentration (Cmax) of Bupropion
timeFrame: 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
measure: Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of Bupropion
timeFrame: 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 outcomes:
measure: Number of Participants With Serious and Non-Serious Adverse Events
timeFrame: Up to 32 days after the last dose
Other outcomes:
measure: Peak Plasma Concentration (Cmax) of Hydroxybupropion
timeFrame: 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
measure: Time of Peak Concentration (Tmax) of Hydroxybupropion
timeFrame: 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
measure: Area Under Concentration-Time Curve up to Last Non-zero Value (AUC0-tn) of Hydroxybupropion
timeFrame: 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
measure: Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of Hydroxybupropion
timeFrame: 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
measure: Half-life (t1/2) of Hydroxybupropion
timeFrame: 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
measure: Trough Plasma Concentration (Ctrough) of ASP2151
timeFrame: 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
measure: Peak Plasma Concentration (Cmax) of ASP2151
timeFrame: 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
measure: Time of Peak Concentration (Tmax) of ASP2151
timeFrame: 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
measure: Area Under the Concentration-time Curve Over the Dosing Interval (AUC0-tau) of ASP2151
timeFrame: 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
measure: Area Under the Concentration-time Curve Extrapolated to Infinite Time (AUC0-∞) of ASP2151
timeFrame: 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
measure: Half-life (t1/2) of ASP2151
timeFrame: 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
measure: Apparent Volume of Distribution (Vd/F) of ASP2151
timeFrame: 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
measure: Apparent Total Body Clearance (CL/F) of ASP2151
timeFrame: 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
measure: Time of Peak Concentration (Tmax) of Bupropion
timeFrame: 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
measure: Area Under the Curve Over up to Last No-zero Value (AUC0-tn) of Bupropion
timeFrame: 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
measure: Half-life (t1/2) of Bupropion
timeFrame: 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
measure: Apparent Volume of Distribution (Vd/F) of Bupropion
timeFrame: 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
measure: Apparent Total Body Clearance (CL/F) of Bupropion
timeFrame: 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
Locations:
city: London
country: United Kingdom
facility: Hammersmith Medicines Research Ltd
Study officials:
References: