Bioequivalence Study of Paroxetine and PAXIL Under Fasting Conditions in Healthy Mexican Participants

An Oral Single-dose, Randomized, Balanced, Open-label, Two-sequence, Two-treatment, Two-period, Crossover Bioequivalence Study of Paroxetine Tablets 20 mg of GlaxoSmithKline Pharmaceuticals S.A, With That of PAXIL (Paroxetine) Tablets 20 mg of GlaxoSmithKline México S.A. de C.V., in Healthy Adult Male and Female Subjects Under Fasting Conditions

This study will be conducted to evaluate and compare the single oral dose bioavailability of Paroxetine manufactured by GlaxoSmithKline (GSK) Pharmaceuticals S.A. for GlaxoSmithKline México, S.A. de C.V. with that of PAXIL® (Paroxetine) of GlaxoSmithKline, México, S.A. de C.V. in healthy, adult, male and female participants under fasting conditions. Maximum 38 participants will be randomized and dosed. The expected duration of this study will be 12 days including 7 days of washout period in-between each dosing. PAXIL is a registered trademark of GSK group of companies.

Study Overview

• Status: Completed
• Conditions: Anxiety Disorders
• Intervention / Treatment: Drug: Paroxetine hydrochloride; Drug: PAXIL (Paroxetine hydrochloride )

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

Study Locations

• Mexico
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 66260
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adult male and female participants aged between 18 and 55 years.
• Participant is a light smoker (someone who smokes 9 or less cigarettes per day) or non- or an ex-smoker (someone who completely stopped smoking for at least 6 months before day 1 of this study).
• With a weight greater than or equal to (>=)50.00 kilograms (kg).
• With a body mass index (BMI) >=18.5 kilograms per meter square (kg/m^2) and less than or equal to (<=)27.0 kg/m^2.
• Found healthy according to the clinical laboratory results and physical examination (performed within 90 days prior to the dosing on period -1).
• Have a normal 12 lead electrocardiogram (ECG) and vital signs.
• Have laboratory test results within the laboratory's stated normal range; if not within this range, they must lack of no clinical significance as judged by the principal investigator (PI) or responsible physician.
• Willing to avoid sexual contact or use an acceptable contraceptive method during the study including the washout period (for females). In case of male participants, they should avoid sexual contact or use a latex or synthetic condom each time they have sex with a woman while taking Paroxetine and during 7 days after the end of the study.
• If study participant is a female and is of child bearing potential, practicing an acceptable method of birth control for the duration of the study as judged by the investigators, like combined short acting (estrogen and progestogen containing) hormonal contraception for example (e.g.) oral, intravaginal, and progestogen-only hormonal contraception e.g. oral, intrauterine device (IUD), intrauterine hormone-releasing system (IUS), condoms, foams, jellies and diaphragm or abstinence or if study participant is a female and is postmenopausal for at-least 1 year or is surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy has been performed on the study participant).
• Have a negative test for active Coronavirus Disease-2019 (COVID-19), within 72 hours prior to the first period check-in. The testing should be done using a molecular (Real time-Polymerase Chain Reaction [RT-PCR]) approved by the country regulatory authorities.
• Participant is able to communicate effectively and voluntarily agreed to participate in this study by signing written informed consent after being informed sufficiently about study aspects like objectives, study procedures, characteristics of the investigational drug, expected adverse events.
• Participant willing to adhere to protocol requirements as described in informed consent (written) approved by research ethics committee/research committee (REC/RC).

Exclusion Criteria:

• If participants age is less than 18 or older than 55 years.
• Have any history of allergy or hypersensitivity to Paroxetine or derivatives to any of its metabolites/derivatives or related drugs or excipients.
• Have a positive test result for hepatitis B surface antigen (HBs Ag) or hepatitis C virus antibody (HCV Ab) or human immune deficiency virus (HIV) antibodies (types 1 and 2) or venereal disease research laboratory (VDRL).
• Participants with symptoms suggestive of active COVID-19 infection (that is, fever, cough, respiratory difficulties) within 14 days of inpatient admission.
• Participants with known COVID-19 positive contact (meaning if the participant has been living, providing care, being within 1.5 meters for at least 15 min or having exposure to respiratory secretions with/to a person who has COVID-19) within the past 14 days prior to the first period check-in. Study drug is contraindicated for medical reasons to the participants.
• Have any history or presence of significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, seizures, endocrine, dermatological, neurological or psychiatric disease or disorder (e.g. participants with uncontrolled hypertension, pheochromocytoma, carcinoid, thyrotoxicosis, bipolar depression, schizoaffective disorder and acute confusional states).
• Presence of significant gastrointestinal, hepatic or kidney disease, or surgery or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects or participants with a history of gastrointestinal disorder or surgery which may affect the absorption of investigational drug.
• Have a history of alcohol abuse or drug abuse during the last 1 year prior to period -1 dosing.
• Have a history of smoking >=10 cigarettes per day during the last 6 months prior to period -1 dosing.
• Have history or presence of cancer.
• Have any history of gastrointestinal ulcers/intestinal bleeding.
• Have history of difficulty for donating blood.
• Have clinically significant abnormal laboratory tests results.
• Have a systolic blood pressure less than (<)90 or greater than (>)140 millimeters of mercury (mmHg) or diastolic blood pressure is <60 or >90 mmHg.
• Have a pulse rate <60 beats/minute or >100 beats/minute (lower range of pulse range will be accepted up to 45 beats/minute in case of athlete).
• Have used any prescribed medication during the last 14 days preceding the first dosing, or use over-the-counter (OTC), medicinal or herbal products during the last 7 days or use medicinal enzyme inhibitors / inducers during last 30 days preceding the first dosing.
• Have participated in a drug research study or donated blood within the last 3 months.
• Have a positive result for drugs of abuse test (cannabinoids [marijuana/tetrahydrocannabinol-(THC)], cocaine, opiates/morphine, amphetamine, methamphetamine and benzodiazepines] performed during screening.
• Female participant, who is currently breast feeding or a who is pregnant or who is likely to become pregnant during the study.
• Female participant has a positive pregnancy test results.
• Unwillingness or inability to comply with the instructions on the lifestyle.
• If the PI considers, for any reason, that the volunteer is not a suitable candidate to receive the study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Paroxetine hydrochloride followed by PAXIL	Drug: Paroxetine hydrochloride; Paroxetine hydrochloride will be administered.; Drug: PAXIL (Paroxetine hydrochloride ); PAXIL will be administered.
Experimental: PAXIL followed by paroxetine hydrochloride	Drug: Paroxetine hydrochloride; Paroxetine hydrochloride will be administered.; Drug: PAXIL (Paroxetine hydrochloride ); PAXIL will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Plasma Concentration (Cmax) of Paroxetine	Blood samples were collected at indicated time points for the analysis of Cmax of Paroxetine. PK parameters were analyzed using non-compartmental analysis.	Pre-dose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours post-dose
Area Under the Concentration-time Curve (AUC) From Time Zero to the Last Measurable Concentration (AUC[0-t]) of Paroxetine	Blood samples were collected at indicated time points for the analysis of AUC(0-t) of Paroxetine. PK parameters were analyzed using non-compartmental analysis.	Pre-dose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours post-dose
Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of Paroxetine	Blood samples were collected at indicated time points for the analysis of AUC(0-inf) of Paroxetine. PK parameters were analyzed using non-compartmental analysis.	Pre-dose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours post-dose
Percentage of AUC (0 to Infinity) Obtained by Extrapolation (%AUCex) of Paroxetine	Blood samples were collected at indicated time points for the analysis of %AUCex of Paroxetine. PK parameters were analyzed using non-compartmental analysis.	Pre-dose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours post-dose
Time of the Maximum Measured Plasma Concentration (Tmax) of Paroxetine	Blood samples were collected at indicated time points for the analysis of Tmax of Paroxetine. PK parameters were analyzed using non-compartmental analysis.	Pre-dose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours post-dose
Elimination Half-life (t1/2) of Paroxetine	Blood samples were collected at indicated time points for the analysis of t1/2 of Paroxetine. PK parameters were analyzed using non-compartmental analysis.	Pre-dose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours post-dose
Terminal Elimination Rate Constant (Kel) of Paroxetine	Blood samples were collected at indicated time points for the analysis of Kel of Paroxetine. PK parameters were analyzed using non-compartmental analysis.	Pre-dose (0 hour) and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 6.5, 7, 8, 9, 10, 12, 16, 24, 36, 48 and 72 hours post-dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)	An adverse event (AE) is any untoward medical occurrence that may occur in a research participant during clinical research phase of a drug or vaccine but which does not necessarily has a causal relationship with this. SAE is defined as any medical occurrence that, at any dose, put participants's life in risk or results in death, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent significant disability/incapacity, is a congenital anomaly/birth defect and other important medical events according to medical or scientific judgement.	Up to 25 days
Number of Participants With Abnormal Vital Signs	Systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse rate, respiration rate and body temperature were measured in semi-supine position after 5 minutes rest. The clinically acceptable range included; SBP: 85 millimeters of mercury (mmHg) to 160 mmHg; DBP: 45 mmHg to 100 mmHg; pulse rate: 40 beats per minute to 110 beats per minute; respiration rate: 8 breaths per minute to 20 breaths per minute; body temperature: 35.5 degrees Celsius to 37.8 degrees Celsius. Number of participants with any abnormality in vital signs are presented. Data is presented treatment wise.	Up to 25 days

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2020
• Primary Completion (Actual): January 2, 2021
• Study Completion (Actual): January 2, 2021

Study Registration Dates

• First Submitted: March 16, 2020
• First Submitted That Met QC Criteria: March 16, 2020
• First Posted (Actual): March 17, 2020

Study Record Updates

• Last Update Posted (Actual): January 20, 2022
• Last Update Submitted That Met QC Criteria: December 21, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Bioequivalence study; Anxiety Disorders; Paroxetine hydrochloride; PAXIL; Fasting condition
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Paroxetine
• Other Study ID Numbers: 212969

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No