Depressive Disorder, Major
Conditions
Keywords
Major depressive disorder, Extended release Bupropion
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.
Interventions
DRUGBupropion HCl XL tablet 150mg
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.
DRUGBupropion HCl XL tablet 300mg
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.
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* 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. * Non-smoking healthy males and females as assessed by medical history and physical examination. Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring. A subject with a clinical abnormality or laboratory parameters which are not specifically listed in the inclusion or
Exclusion criteria
, outside the reference range for the population being studied may be included only if the Investigator agree and document that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the concentration-time curve over the dosing interval (AUC [0-tau]) in plasma of Bupropion HCl and its metabolites after repeated dose. | Day 5 to Day 19. | 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). |
| Time taken to reach peak plasma concentration (Tmax) of Bupropion HCl and its metabolites after single dose. | Day 1 and Day 2. | Blood sample will be collected at pre-dosing, and 2, 3, 4, 5, 6, 8, 12, 16, and 24 hour (h) post dose. |
| Tmax in plasma of Bupropion HCl and its metabolites after repeated doses | Day 5 to Day 19 . | 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). |
| Maximum observed concentration (Cmax) in plasma of Bupropion HCl and its metabolites after single dose. | Day 1 and Day 2. | Blood sample will be collected at pre-dosing, and 2, 3, 4, 5, 6, 8, 12, 16, and 24 h post dose. |
| 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. | Day 1 and Day 2. | Blood sample will be collected at pre-dosing, and 2, 3, 4, 5, 6, 8, 12, 16, and 24 h post dose. |
| 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. | Day 5 to Day 19. | 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). |
| Elimination half-life (t ½) in plasma of Bupropion HCl and its metabolites after repeated dose. | Day 5 to Day 19. | 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). |
| Apparent clearance (CL/F) in plasma of Bupropion HCl and its metabolites after repeated dose. | Day 5 to Day 19. | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with adverse event (AE) and serious adverse event (SAE). | Up to Day 33. | An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as SAE. |
| Number of subjects with abnormal Haematology parameters as a measure of safety. | Up to Day 19. | Blood sample will be collected at screening, Day 1, Day 6 and Day 19 to assess platelet counts, red blood cells (RBC) count, haemoglobin, hematocrit, white blood cells (WBC) count, reticulocyte count, mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), composite of WBC differential counts. |
| Number of subjects with abnormal Clinical chemistry parameters as a measure of safety. | Up to Day 19. | Blood sample will be collected at screening, Day 1, Day 6 and Day 19 to analyze blood urea nitrogen (BUN), creatinine, lactate dehydrogenase (LDH), urea, glucose level (fasting), composite electrolytes levels, gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT), alkaline phosphatase (ALP) levels, total cholesterol, total and direct bilirubin, uric acid, total protein and albumin levels. |
| Number of subjects with abnormal Urinalysis parameters as a measure of safety assessed by dipstick test. | Up to Day 19. | Urine sample will be collected at screening, Day 1, Day 6 and Day 19 to analyze specific gravity, pH, glucose, protein, blood and ketone bodies, and microscopic examination. |
| Body temperature assessment as a safety measure. | Day 0 to Day 13. | Body temperature will be measured at screening, Day 0, Day 4 and Day 13 and sometimes when clinically indicated. |
| Blood pressure assessment as a safety measure. | Day 1 to Day 19. | Clinostatic hypertension (CH) will be measured which is defined as a group of patients presenting an increase in arterial blood pressure when supine and a concurrent decrease of at least 20 millimetre of mercury (mm Hg) of Systolic blood pressure (SBP) and/or at least 10 mm Hg of Diastolic blood pressure (DBP) upon standing. SBP and DBP will be measured pre-dosing and at 2, 4, 8h post-dosing on Day 1; pre-dosing and at 2, 5, 8h post-dosing on Day 6; after discharge on Day 2, 7 and 16; post dosing on the Day 3, 5, 9, 11, 14 and 19 or early withdraw from the study. |
| Heart rate assessment as a safety measure. | Day 1 to Day 19. | Heart rate will be measured pre-dosing and at 2, 4, 8h post-dosing on Day 1; pre-dosing and at 2, 5, 8h post-dosing on Day 6; after discharge on Day 2, 7 and 16; post dosing on the Day 3, 5, 9, 11, 14 and 19 or early withdraw from the study. |
| Electrocardiogram (ECG) assessment as a measure of safety and tolerability. | Screening and Day 19. | 12-lead ECGs will be obtained. |
Countries
China
Outcome results
None listed