Clinical trial NCT03329573: Bioequivalence Study of Paroxetine Immediate Release (IR) Tablets Manufactured in GlaxoSmithKline Tianjin (GSKT) and Mississauga Sites in Healthy Chinese Subjects
Official title: Randomized, Open Label, 2-way Crossover, Single Dose Bioequivalence Study of Paroxetine IR Tablets Manufactured in GSKT and Mississauga Sites in Healthy Chinese Participants Under Fasting and Fed Conditions
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Anxiety Disorders
Keywords: Cross-over
Chinese
GSKT
Mississauga
Healthy
Bioequivalence
Paroxetine
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2017-11-06
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: In this study, each subject will receive paroxetine IR 40mg A or B in a cross-over manner
Primary purpose: TREATMENT

Brief summary: Paroxetine is a selective serotonin reuptake inhibitor (SSRI) and paroxetine IR tablets have been approved for the treatment of three anxiety indications in China. This bioequivalence study will evaluate Paroxetine IR tablets manufactured in GSKT (A) and Mississauga (B) sites in healthy Chinese subjects under fasting and fed conditions to support the quality consistency evaluation. This is a single dose, open-label, randomized, two-period crossover study and will include a screening period (up to 7 days), two open-label treatment periods (up to 16 days) and a follow-up phase (up to 14 days after last-dose). The whole study will be divided into two groups, one for fasting condition enrolling approximately 36 subjects and another for fed condition for which approximately 44 subjects will be enrolled. In both groups, eligible subjects will be randomized to receive single dose of Paroxetine IR tablets A or B in a cross-over manner.


Eligibility criteria: 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 (in consultation with the GSK Medical Monitor if necessary) 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) (male) or 45kg(female) and Body mass index (BMI) 19.0 to 26.0 kg per meter square (kg/m\^2) (inclusive).
* 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 one of the defined contraception method during the study and until follow up contact.
* Male Subjects with female partners of child-bearing potential must agree to use one of the defined 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 bundlebranch block.

Exclusion Criteria:

* 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 one year of the study defined as: an average weekly intake of \>14 drinks. One drink is equivalent to 12 grams (g) of alcohol: 12 ounces \[360 milliliter (mL)\] 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 ECG, hematology, 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 Suicide Severity Rating 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.
* Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
* Unable to refrain from the use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study medication.
* In subjects with concomitant use of monoamine oxidase inhibitors (MAOIs) (including linezolid, an antibiotic which is a reversible non-selective MAOIs and methylthioninium chloride (methylene blue)) or within two weeks of terminating treatment with MAOIs.
* In subjects with concomitant use of thioridazine or pimozide.
* The subject has participated in a clinical trial and has received an investigational product within 90 days prior to the first dosing day in the current study, or has participated in a clinical trial without receiving any investigational product within 30 days prior to the first dosing day in the current study.
* A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months.
* Serum human immuno-deficiency virus (HIV) antibody or Syphilis antibody positive.
* A positive pre-study drug/alcohol screen.
* Known allergy to paroxetine IR Tablets or any of its components.
* Blood donation in excess of 400 mL in the 3 months prior to enrolment.
* Obvious evidence of active hematological diseases, or significant blood loss in the last 3 months. History of sensitivity to heparin or heparin-induced thrombocytopenia.
* Lactating females or women of child bearing potential used oral or implanted contraceptives within the 30 days prior to enrolment, or received injections of chronically acting contraceptives in the 1 year prior to study initiation.
* Other conditions which, in the Investigator's judgment, render subjects unsuitable for the clinical study.

Primary outcomes:
measure: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinite Time (AUC[0-infinity]) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition
timeFrame: Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
measure: AUC(0-infinity) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition
timeFrame: Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
measure: Area Under the Concentration-time Curve From Administration Extrapolated to the Last Time of Quantifiable Concentration (AUC[0-t]) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition
timeFrame: Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
measure: AUC(0-t) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition
timeFrame: Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
measure: Maximum Observed Concentration (Cmax) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition
timeFrame: Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
measure: Cmax of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition
timeFrame: Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
Secondary outcomes:
measure: Time to Reach Maximum Observed Concentration (Tmax) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition
timeFrame: Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
measure: Tmax of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition
timeFrame: Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
measure: Terminal Elimination Rate Constant (Lambda z) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition
timeFrame: Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
measure: Lambda z of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition
timeFrame: Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
measure: Terminal Elimination Half-life (t1/2) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition
timeFrame: Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
measure: t1/2 of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition
timeFrame: Pre-dose, 0.5 hour, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 10 hours, 12 hours, 16 hours, 24 hours, 36 hours, 48 hours, 72 hours and 96 hours post-dose in each treatment period
measure: Number of Participants With Non-serious Adverse Events and Serious Adverse Events (SAEs) Under Fed Condition
timeFrame: Up to Day 26
measure: Number of Participants With Non-SAE and SAEs Under Fasting Condition
timeFrame: Up to Day 26
measure: Number of Participants With Chemistry Laboratory Values Relative to Potential Clinical Importance (PCI) Criteria on Day 16 Under Fed Condition
timeFrame: Day 16
measure: Number of Participants With Chemistry Laboratory Values Relative to PCI Criteria on Day 16 Under Fasting Condition
timeFrame: Day 16
measure: Number of Participants With Hematology Laboratory Values Relative to PCI Criteria on Day 16 Under Fed Condition
timeFrame: Day 16
measure: Number of Participants With Hematology Laboratory Values Relative to PCI Criteria on Day 16 Under Fasting Condition
timeFrame: Day 16
measure: Number of Participants With Urinalysis Results by Dipstick Method Under Fed Condition
timeFrame: Baseline (Day-7 to Day -1) and Day 16
measure: Number of Participants With Urinalysis Results by Dipstick Method Under Fasting Condition
timeFrame: Baseline (Day-7 to Day -1) and Day 16
measure: Number of Participants With Clinically Significant Abnormal Findings for Electrocardiogram (ECG) Parameters Under Fed Condition
timeFrame: Baseline (Day-7 to Day -1) and Day 16
measure: Number of Participants With Clinically Significant Abnormal Findings for ECG Parameters Under Fasting Condition
timeFrame: Baseline (Day-7 to Day -1) and Day 16
measure: Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) at Indicated Time-points Under Fed Condition
timeFrame: Day 1 (post-dose), Day 2 (post-dose), Day 3, Day 4, Day 5, Day 11, Day 12 (pre-dose), Day 12 (post-dose), Day 13 (post-dose), Day 14, Day 15, Day 16
measure: DBP and SBP at Indicated Time-points Under Fasting Condition
timeFrame: Day 1 (post-dose), Day 2 (post-dose), Day 3, Day 4, Day 5, Day 11, Day 12 (pre-dose), Day 12 (post-dose), Day 13 (post-dose), Day 14, Day 15, Day 16
measure: Pulse Rate (PR) at Indicated Time-points Under Fed Condition
timeFrame: Day 1 (post-dose), Day 2 (post-dose), Day 3, Day 4, Day 5, Day 11, Day 12 (pre-dose), Day 12 (post-dose), Day 13 (post-dose), Day 14, Day 15, Day 16
measure: Pulse Rate (PR) at Indicated Time-points Under Fasting Condition
timeFrame: Day 1 (post-dose), Day 2 (post-dose), Day 3, Day 4, Day 5, Day 11, Day 12 (pre-dose), Day 12 (post-dose), Day 13 (post-dose), Day 14, Day 15, Day 16
measure: Respiratory Rate (RR) at Indicated Time-point Under Fed Condition
timeFrame: Day 11
measure: RR at Indicated Time-point Under Fasting Condition
timeFrame: Day 11
measure: Temperature at Indicated Time-point Under Fed Condition
timeFrame: Day 11
measure: Temperature at Indicated Time-point Under Fasting Condition
timeFrame: Day 11
Other outcomes:
Locations:
city: Shanghai
country: China
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: