Bioequivalence Study of Paroxetine Immediate Release (IR) Tablets Manufactured in GlaxoSmithKline Tianjin (GSKT) and Mississauga Sites in Healthy Chinese Subjects

NCT03329573 | Completed Phase 1 Results

• 1 other identifier: 207652
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

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.

Conditions

Anxiety Disorders

Keywords

Cross-over; Chinese; GSKT; Mississauga; Healthy; Bioequivalence; Paroxetine

Outcome Measures

Primary Outcomes (6)

• 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

  Blood samples were collected at designated time points. Pharmacokinetic (PK) parameters of Paroxetine were calculated using non-compartmental methods. Statistical analysis of PK parameters was done using mixed effect model for evaluation of bioequivalence (BE). Point estimate and associated adjusted 90% confidence interval (CI) of difference between both the treatments were provided for AUC(0-infinity).

  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

• AUC(0-infinity) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition

  Blood samples were collected at designated timepoints. PK parameters of Paroxetine were calculated using non-compartmental methods. Statistical analysis of PK parameters was done using mixed effect model for evaluation of BE. Point estimate and associated adjusted 90% CI of difference between both the treatments were provided for AUC(0-infinity).

  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

• 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

  Blood samples were collected at designated timepoints. PK parameters of Paroxetine were calculated using non-compartmental methods. Statistical analysis of PK parameters was done using mixed effect model for evaluation of BE. Point estimate and associated adjusted 90% CI of difference between both the treatments were provided for AUC(0-t).

  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

• AUC(0-t) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition

  Blood samples were collected at designated timepoints. PK parameters of Paroxetine were calculated using non-compartmental methods. Statistical analysis of PK parameters was done using mixed effect model for evaluation of BE. Point estimate and associated adjusted 90% CI of difference between both the treatments were provided for AUC(0-t).

  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

• Maximum Observed Concentration (Cmax) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition

  Blood samples were collected at designated timepoints. PK parameters of Paroxetine were calculated using non-compartmental methods. Statistical analysis of PK parameters was done using mixed effect model for evaluation of BE. Point estimate and associated adjusted 90% CI of difference between both the treatments were provided for Cmax.

  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

• Cmax of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition

  Blood samples were collected at designated timepoints. PK parameters of Paroxetine were calculated using non-compartmental methods. Statistical analysis of PK parameters was done using mixed effect model for evaluation of BE. Point estimate and associated adjusted 90% CI of difference between both the treatments were provided for Cmax.

  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 (24)

• Time to Reach Maximum Observed Concentration (Tmax) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition

  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

• Tmax of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition

  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

• Terminal Elimination Rate Constant (Lambda z) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition

  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

• Lambda z of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition

  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

• Terminal Elimination Half-life (t1/2) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition

  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

Study Arms (4)

AB treatment sequence receivers in fasting group

EXPERIMENTAL

Eligible subjects will receive a single dose of Paroxetine IR tablets A in Period 1 followed by Paroxetine IR tablets B in Period 2 in fasting state.

Drug: Paroxetine IR tablets A; Drug: Paroxetine IR tablets B

BA treatment sequence receivers in fasting group

EXPERIMENTAL

Eligible subjects will receive a single dose of Paroxetine IR tablets B in Period 1 followed by Paroxetine IR tablets A in Period 2 in fasting state.

Drug: Paroxetine IR tablets A; Drug: Paroxetine IR tablets B

AB treatment sequence receivers in fed group

EXPERIMENTAL

Eligible subjects will receive a single dose of Paroxetine IR tablets A in Period 1 followed by Paroxetine IR tablets B in Period 2 in fed state.

Drug: Paroxetine IR tablets A; Drug: Paroxetine IR tablets B

BA treatment sequence receivers in fed group

EXPERIMENTAL

Eligible subjects will receive a single dose of Paroxetine IR tablets B in Period 1 followed by Paroxetine IR tablets A in Period 2 in fed state.

Drug: Paroxetine IR tablets A; Drug: Paroxetine IR tablets B

Interventions

Paroxetine IR tablets A DRUG

Paroxetine IR tablets A will be the investigational drug. These are film coated tablets with unit dose strength of 20 milligrams (mg) and will be administered via oral route. These tablets will be manufactured in GSKT.

AB treatment sequence receivers in fasting group; AB treatment sequence receivers in fed group; BA treatment sequence receivers in fasting group; BA treatment sequence receivers in fed group

Paroxetine IR tablets B DRUG

Paroxetine IR tablets B will be the reference drug. These are film coated tablets with unit dose strength of 20 mg and will be administered via oral route. These tablets will be manufactured in Mississauga.

AB treatment sequence receivers in fasting group; AB treatment sequence receivers in fed group; BA treatment sequence receivers in fasting group; BA treatment sequence receivers in fed group

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) (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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Shanghai, 201508, China

Location

MeSH Terms

Conditions

Anxiety Disorders

Condition Hierarchy (Ancestors)

Mental Disorders

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: This study is an open-label treatment period; hence, masking will not be performed.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In this study, each subject will receive paroxetine IR 40mg A or B in a cross-over manner

Study Record Dates

• First Submitted: October 30, 2017
• First Posted: November 6, 2017
• Study Start: May 30, 2018
• Primary Completion: August 3, 2018
• Study Completion: August 3, 2018
• Last Updated: March 27, 2020
• Results First Posted: August 19, 2019

Record last verified: 2020-03

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)