Phase 1
Completed N=85
Bioequivalence Study of Paroxetine Immediate Release (IR) Tablets Manufactured in GlaxoSmithKline Tianjin (GSKT) and Mississauga Sites in Healthy Chinese Subjects
Source: ClinicalTrials.gov NCT03329573 ↗Enrolled (actual)
85
Serious AEs
0.0%
Results posted
Aug 2019
Primary outcomePrimary: 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 — 860.54; 812.49 Hour*nanogram per milliliter
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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 |
860.54; 812.49 | — |
| PRIMARY AUC(0-infinity) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition |
742.07; 745.22 | — |
| PRIMARY 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 |
866.85; 814.75 | — |
| PRIMARY AUC(0-t) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition |
750.49; 753.83 | — |
| PRIMARY Maximum Observed Concentration (Cmax) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition |
39.95; 39.02 | — |
| PRIMARY Cmax of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition |
36.86; 36.15 | — |
| SECONDARY Time to Reach Maximum Observed Concentration (Tmax) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition |
5.00; 5.00 | — |
| SECONDARY Tmax of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition |
5.00; 5.00 | — |
| SECONDARY Terminal Elimination Rate Constant (Lambda z) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition |
0.0433; 0.0462 | — |
| SECONDARY Lambda z of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition |
0.0483; 0.0494 | — |
| SECONDARY Terminal Elimination Half-life (t1/2) of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fed Condition |
16.0002; 14.9913 | — |
| SECONDARY t1/2 of Paroxetine Following Single Oral Dose in Healthy Chinese Participants Under Fasting Condition |
14.3515; 14.0311 | — |
| SECONDARY Number of Participants With Non-serious Adverse Events and Serious Adverse Events (SAEs) Under Fed Condition |
14; 13; 0; 0 | — |
| SECONDARY Number of Participants With Non-SAE and SAEs Under Fasting Condition |
12; 16; 0; 0 | — |
| SECONDARY Number of Participants With Chemistry Laboratory Values Relative to Potential Clinical Importance (PCI) Criteria on Day 16 Under Fed Condition |
0; 0; 22; 22; 0; 0 | — |
| SECONDARY Number of Participants With Chemistry Laboratory Values Relative to PCI Criteria on Day 16 Under Fasting Condition |
0; 0; 19; 19; 0; 0 | — |
| SECONDARY Number of Participants With Hematology Laboratory Values Relative to PCI Criteria on Day 16 Under Fed Condition |
2; 2; 20; 19; 0; 1 | — |
| SECONDARY Number of Participants With Hematology Laboratory Values Relative to PCI Criteria on Day 16 Under Fasting Condition |
1; 0; 18; 19; 0; 0 | — |
| SECONDARY Number of Participants With Urinalysis Results by Dipstick Method Under Fed Condition |
22; 25; 0; 0; 22; 22 | — |
| SECONDARY Number of Participants With Urinalysis Results by Dipstick Method Under Fasting Condition |
19; 19; 0; 0; 19; 19 | — |
| SECONDARY Number of Participants With Clinically Significant Abnormal Findings for Electrocardiogram (ECG) Parameters Under Fed Condition |
0; 0; 1; 0 | — |
| SECONDARY Number of Participants With Clinically Significant Abnormal Findings for ECG Parameters Under Fasting Condition |
0; 0; 0; 0 | — |
| SECONDARY Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) at Indicated Time-points Under Fed Condition |
70.4; 67.8; 69.0; 66.8; 67.7; 64.5 | — |
| SECONDARY DBP and SBP at Indicated Time-points Under Fasting Condition |
71.8; 70.9; 68.3; 68.7; 66.2; 67.8 | — |
| SECONDARY Pulse Rate (PR) at Indicated Time-points Under Fed Condition |
72.3; 72.0; 72.8; 74.1; 74.0; 75.8 | — |
| SECONDARY Pulse Rate (PR) at Indicated Time-points Under Fasting Condition |
65.4; 67.5; 74.8; 75.3; 74.9; 77.2 | — |
| SECONDARY Respiratory Rate (RR) at Indicated Time-point Under Fed Condition |
17.8; 18.6 | — |
| SECONDARY RR at Indicated Time-point Under Fasting Condition |
19.2; 19.4 | — |
| SECONDARY Temperature at Indicated Time-point Under Fed Condition |
36.70; 36.59 | — |
| SECONDARY Temperature at Indicated Time-point Under Fasting Condition |
36.84; 36.74 | — |
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 ULN is acceptable if bilirubin is fractionated and direct bilirubin 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
Data sourced from ClinicalTrials.gov (NCT03329573). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.