Clinical trial NCT04311463: Bioequivalence Study of Paroxetine and PAXIL Under Fasting Conditions in Healthy Mexican Participants
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Anxiety Disorders
Keywords: Anxiety Disorders
Bioequivalence study
Paroxetine hydrochloride
PAXIL
Fasting condition
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2020-03-17
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: A single-dose, randomized, balanced, open-label, two-sequence, two-treatment, two-period, crossover bioequivalence study under fasting condition.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of Paroxetine
timeFrame: 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
measure: Area Under the Concentration-time Curve (AUC) From Time Zero to the Last Measurable Concentration (AUC[0-t]) of Paroxetine
timeFrame: 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
measure: Area Under the Concentration Versus Time Curve From Time Zero to Infinity (AUC[0-inf]) of Paroxetine
timeFrame: 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
measure: Percentage of AUC (0 to Infinity) Obtained by Extrapolation (%AUCex) of Paroxetine
timeFrame: 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
measure: Time of the Maximum Measured Plasma Concentration (Tmax) of Paroxetine
timeFrame: 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
measure: Elimination Half-life (t1/2) of Paroxetine
timeFrame: 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
measure: Terminal Elimination Rate Constant (Kel) of Paroxetine
timeFrame: 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:
measure: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Up to 25 days
measure: Number of Participants With Abnormal Vital Signs
timeFrame: Up to 25 days
Other outcomes:
Locations:
city: Monterrey
country: Mexico
facility: GSK Investigational Site
state: Nuevo León
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: