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

NCT04311463 | Completed Phase 1 Results

• 1 other identifier: 212969
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Anxiety Disorders

Keywords

Anxiety Disorders; Bioequivalence study; Paroxetine hydrochloride; PAXIL; Fasting condition

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (2)

• Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to 25 days

• Number of Participants With Abnormal Vital Signs

  Up to 25 days

Study Arms (2)

Paroxetine hydrochloride followed by PAXIL

EXPERIMENTAL

Drug: Paroxetine hydrochloride; Drug: PAXIL (Paroxetine hydrochloride )

PAXIL followed by paroxetine hydrochloride

EXPERIMENTAL

Drug: Paroxetine hydrochloride; Drug: PAXIL (Paroxetine hydrochloride )

Interventions

Paroxetine hydrochloride DRUG

Paroxetine hydrochloride will be administered.

PAXIL followed by paroxetine hydrochloride; Paroxetine hydrochloride followed by PAXIL

PAXIL (Paroxetine hydrochloride ) DRUG

PAXIL will be administered.

PAXIL followed by paroxetine hydrochloride; Paroxetine hydrochloride followed by PAXIL

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Monterrey, Nuevo León, 66260, Mexico

Location

MeSH Terms

Conditions

Anxiety Disorders

Interventions

Paroxetine

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

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 is an open-label study.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A single-dose, randomized, balanced, open-label, two-sequence, two-treatment, two-period, crossover bioequivalence study under fasting condition.

Study Record Dates

• First Submitted: March 16, 2020
• First Posted: March 17, 2020
• Study Start: December 9, 2020
• Primary Completion: January 2, 2021
• Study Completion: January 2, 2021
• Last Updated: January 20, 2022
• Results First Posted: January 20, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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

ME (1)