A Study to Evaluate Pharmacokinetics, Safety and Tolerability of Extended-release Bupropion Hydrochloride Tablets in Chinese Healthy Volunteers

NCT02698553 | Completed Phase 1

• 1 other identifier: 114883
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Bupropion is used in psychological disorder mainly in major depressive disorder (MDD). In China, buproprion Immediate Release (IR) and Sustained Release (SR) tablet have been in market for the treatment of MDD. Bupropion Hydrochloride (HCl) Extended Release (XL) tablets formulation is proposed for marketing approval in China for same indication. Therefore, a pharmacokinetic study is planned to be conducted in Chinese subjects. It is an open label, single-centre and single cycle study to evaluate the pharmacokinetics, safety and tolerability of 150 milligram (mg) and 300 mg following single and repeated daily doses. Approximately 16 males and females Chinese healthy subjects will be enrolled into the study to get 12 completed subjects.

Conditions

Depressive Disorder, Major

Keywords

Major depressive disorder; Extended release Bupropion

Outcome Measures

Primary Outcomes (8)

• Time taken to reach peak plasma concentration (Tmax) of Bupropion HCl and its metabolites after single dose.

  Blood sample will be collected at pre-dosing, and 2, 3, 4, 5, 6, 8, 12, 16, and 24 hour (h) post dose.

  Day 1 and Day 2.

• Maximum observed concentration (Cmax) in plasma of Bupropion HCl and its metabolites after single dose.

  Blood sample will be collected at pre-dosing, and 2, 3, 4, 5, 6, 8, 12, 16, and 24 h post dose.

  Day 1 and Day 2.

• Area under the plasma concentration-time curve from time 0 to 24 hours (AUC [0-24]) of Bupropion HCl and its metabolites after single dose.

  Blood sample will be collected at pre-dosing, and 2, 3, 4, 5, 6, 8, 12, 16, and 24 h post dose.

  Day 1 and Day 2.

• Tmax in plasma of Bupropion HCl and its metabolites after repeated doses

  Blood sample will be collected at pre-dosing, and 2, 5, 8 and 12h post dose after 150 mg dose (Day 5) and first 300 mg (Day 6) dose respectively. Blood sample will be also collected at pre-dosing, and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96 and 120 h post dose after 300 mg dose (Day 14 to 19).

  Day 5 to Day 19 .

• Steady state concentration (Css)-Css Minimum (Css_min), Css Maximum (Css_max), Average Css (Css_av) in plasma of Bupropion HCl and its metabolites after repeated dose.

  Blood sample will be collected at pre-dosing, and 2, 5, 8 and 12h post dose after 150 mg dose (Day 5) and first 300 mg (Day 6) dose respectively, and pre-dosing, and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96 and 120 h post dose after last 300 mg dose (Day 14 to 19).

  Day 5 to Day 19.

• Elimination half-life (t ½) in plasma of Bupropion HCl and its metabolites after repeated dose.

  Blood sample will be collected at pre-dosing, and 2, 5, 8 and 12 h post dose after 150 mg dose (Day 5) and first 300 mg (Day 6) dose respectively, and pre-dosing, and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96 and 120 h post dose after last 300 mg dose (Day 14 to 19).

  Day 5 to Day 19.

• Apparent clearance (CL/F) in plasma of Bupropion HCl and its metabolites after repeated dose.

  Blood sample will be collected at pre-dosing, and 2, 5, 8 and 12 h post dose after last 150 mg dose (Day 5) and first 300 mg (Day 6) dose respectively, and pre-dosing, and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96 and 120 h post dose after last 300 mg dose (Day 14 to 19).

  Day 5 to Day 19.

• Area under the concentration-time curve over the dosing interval (AUC [0-tau]) in plasma of Bupropion HCl and its metabolites after repeated dose.

  Blood sample will be collected at pre-dosing, and 2, 5, 8 and 12 h post dose after 150 mg dose (Day 5) and first 300 mg (Day 6) dose respectively, and pre-dosing, and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, 72, 96 and 120 h post dose after last 300 mg dose (Day 14 to 19).

  Day 5 to Day 19.

Secondary Outcomes (8)

• Number of subjects with adverse event (AE) and serious adverse event (SAE).

  Up to Day 33.

• Number of subjects with abnormal Haematology parameters as a measure of safety.

  Up to Day 19.

• Number of subjects with abnormal Clinical chemistry parameters as a measure of safety.

  Up to Day 19.

• Number of subjects with abnormal Urinalysis parameters as a measure of safety assessed by dipstick test.

  Up to Day 19.

• Body temperature assessment as a safety measure.

  Day 0 to Day 13.

Study Arms (1)

Bupropion XL once daily

EXPERIMENTAL

Healthy subjects will receive Bupropion XL 150milligram (mg) once daily for 5 days (Day 1 to Day 5) and then Bupropion XL 300 mg once daily from Day 6 to Day 14.

Drug: Bupropion HCl XL tablet 150mg; Drug: Bupropion HCl XL tablet 300mg

Interventions

Bupropion HCl XL tablet 150mg DRUG

The 150 mg of tablet will be given to subject once daily orally. Subject will be instructed to swallow whole tablet with 240 ml of water, without crushed, divided or chewed.

Bupropion XL once daily

Bupropion HCl XL tablet 300mg DRUG

The 300 mg of tablet will be given to subject once daily orally. Subject will be instructed to swallow whole tablet with 240 ml of water, without crushed, divided or chewed.

Bupropion XL once daily

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able to actively communicate with the investigator and to complete the study-related documents; able to understand the contents of the Informed consent form (ICF) and to sign a written ICF prior to any study-specific procedures.
• Males and females aged between 18 and 45 years inclusive, at the time of signing the informed consent.

You may not qualify if:

• Body weight\>=50 kilograms (Kg) and Body mass index (BMI) 19.0 to 25.0 kg/square meter (m\^2).
• A female subject is eligible to participate if she is of: Child-bearing potential with negative pregnancy test as determined by serum or urine human chorionic gonadotropin (hCG) test at screening or prior to dosing and agrees to use the contraception methods during the study and until follow up contact.
• Male subjects with female partners of child-bearing potential must agree to use the contraception methods during the study and until follow up contact.
• ALT, ALP and total bilirubin =\<1.5x upper limit of normal (ULN) (isolated bilirubin \>1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35 percent \[%\]).
• Based on single or averaged corrected QT interval (QTc) values of triplicate ECGs obtained over a brief recording period: QTc \<450 milliseconds (msec) or QTc \<480 msec in subjects with bundle branch block.
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
• Drug or alcohol abuse or dependency within one year prior to enrolment. History of regular alcohol consumption within 6 months of the study, defined as: an average weekly intake of \>14 drinks. One drink is equivalent to 12 gram (g) of alcohol: 12 ounces (360 millilitre \[ml\]) of beer, 5 ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 proof distilled spirits.
• Unstable disease conditions; any laboratory measurements assessed by the investigator as clinically relevant (including electroencephalogram \[EEG\], ECG, haematology, biochemistry and urine analysis, etc.); any disorder that might interfere with the absorption, distribution, metabolism or excretion of the study drug; or in the investigator's opinion the disease may lead to safety concerns or interfere with the pharmacokinetics assessment.
• Subjects with concurrent or previous neuropsychological disorders, as assessed by Columbia Suicidality Severity Rating (CSSR) Scale or by the investigator, have suicidal tendency, or have committed suicidal behavior/attempt.
• Known history of cerebral trauma, previous cerebral disorders, seizures or eating disorder, and other conditions that in the investigator's opinion may increase the risk of seizures.
• A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of Other Criteria
• Serum human immunodeficiency virus (HIV) antibody or Syphilis antibody positive.
• A positive pre-study drug/alcohol screen.
• Blood donation in the 3 months prior to enrolment. Where participation in the study would result in donation of blood or blood products in excess of 500 ml within a 56 day period.
• Obvious evidence of active haematological diseases, or significant blood loss in the last 3 months. History of sensitivity to heparin or heparin-induced thrombocytopenia.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Shanghai, 200030, China

Location

Related Publications (1)

• Zhang F, Li Y, Hu J, Zhong J, Li H. Population Pharmacokinetics, Safety and Tolerability of Extended-Release Bupropion and Its Three Metabolites in Chinese Healthy Volunteers. Eur J Drug Metab Pharmacokinet. 2019 Jun;44(3):339-352. doi: 10.1007/s13318-018-0537-z.

  PMID: 30520001 DERIVED

Related Links

• Results for study 114883 can be found on the GSK Clinical Study Register.

MeSH Terms

Conditions

Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 29, 2016
• First Posted: March 3, 2016
• Study Start: May 23, 2016
• Primary Completion: June 29, 2016
• Study Completion: June 29, 2016
• Last Updated: September 13, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

CN (1)