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Phase 1 Completed N=14 Randomized Treatment

A Study to Compare the Relative Bioavailability of Two Different Formulations of GSK3640254

Source: ClinicalTrials.gov NCT03575962 ↗
Enrolled (actual)
14
Serious AEs
0.0%
Results posted
Sep 2019
Primary outcomePrimary: Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) of GSK3640254 Following Single Oral Dose in Healthy Participants — 23.5666; 27.6204 Hour*microgram per milliliter

Summary

This is a first time in human (FTIH), 2-period study, to assess the relative bioavailability of a mesylate salt capsule of GSK3640254, compared to a bis- hydrochloride salt capsule of GSK3640254, in healthy subjects, administered following a moderate calorie and fat meal. The subjects will be randomized to 2 sequences, Regimen AB or Regimen BA. For Regimen AB: The Regimen A, which will include oral administration of GSK3640254 bis-hydrochloride Capsule 200 milligram (mg) (reference), which will be administered, in Period 1 and Regimen B will include GSK3640254 Mesylate salt capsule (test), 200 mg, which will be administered in Period 2. For the regimen BA, the regimen B, will be administered, in Period 1 and regimen A, in Period 2. Each of the regimens will be given orally as 2 capsules in the morning, as per randomization sequence. There will be a minimum washout of 7 days between each dose of study treatment. A total, of 14 subjects, are planned to be enrolled in the study. The maximum duration of the study from screening to follow-up is approximately 7 weeks.

Outcome Measures

OutcomeResultp-value
PRIMARY
Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) of GSK3640254 Following Single Oral Dose in Healthy Participants
23.5666; 27.6204
PRIMARY
Area Under the Concentration-time Curve From Zero to Time of Last Sample Taken (AUC[0-t]) of GSK3640254 Following Single Oral Dose in Healthy Participants
20.2797; 22.6494
PRIMARY
Maximum Observed Concentration (Cmax) of GSK3640254 Following Single Oral Dose in Healthy Participants
0.7357; 0.8502
PRIMARY
Time to Reach Maximum Observed Concentration (Tmax) of GSK3640254 Following Single Oral Dose in Healthy Participants
5.0; 5.0
PRIMARY
Concentration at 24 Hours Post-dose (C24h) of GSK3640254 Following Single Oral Dose in Healthy Participants
0.3439; 0.3855
SECONDARY
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
4; 6; 0; 0
SECONDARY
Change From Baseline in Clinical Chemistry Parameters; Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST)
-1.9; 2.3; -1.2; 3.0; -3.5; -2.9
SECONDARY
Change From Baseline in Clinical Chemistry Parameters; Bicarbonate, Calcium, Chloride, Glucose (Fasting), Potassium, Sodium and Urea
-3.0; -2.6; -0.044; 0.033; -0.5; -1.7
SECONDARY
Change From Baseline in Clinical Chemistry Parameters; Bilirubin, Creatinine and Direct Bilirubin
2.1; -0.3; 0.1; -0.1; -1.0
SECONDARY
Change From Baseline in Clinical Chemistry Parameter; Protein
-0.5; 1.4
SECONDARY
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
0; 0; 14; 14; 0; 0
SECONDARY
Number of Participants With Urinalysis Results by Dipstick Method by Visit
14; 14; 0; 0; 0; 0
SECONDARY
Number of Participants With Clinically Significant Abnormal Findings for Electrocardiogram (ECG) Parameters
0; 0; 0; 0; 0; 0
SECONDARY
Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) at Indicated Time-points
64.6; 64.9; 69.4; 66.1; 63.4; 62.7
SECONDARY
Pulse Rate (PR) at Indicated Time-points
58.1; 58.4; 57.1; 56.9; 61.5; 60.1
SECONDARY
Respiratory Rate (RR) at Indicated Time-points
15.7; 14.7; 14.7; 15.8; 15.4; 15.3
SECONDARY
Temperature at Indicated Time-points
36.74; 36.67; 36.63; 36.59; 36.66; 36.64
SECONDARY
Number of Participants With the Indicated Assessment Events of Suicidal Behavior (SB) and Suicidal Ideation (SI) Via the Columbia Suicide Severity Rating Scale (C-SSRS)
0; 0; 0; 0; 0; 0

Eligibility Criteria

Inclusion Criteria

  • Subject must be 18 to 55 years of age inclusive, at the time of signing the informed consent
  • Subjects who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
  • Body weight >= 50 kilogram (kg) for men and >= 45 kg for women, and body mass index (BMI) within the range 19.0 to 32.0 kg per meter square (kg/m^2) (inclusive).
  • Male or female subjects, where a male subject must agree to use contraception, during the treatment period and for at least 14-weeks following the last dose, corresponding to the time needed to eliminate study treatment for potential genotoxic and teratogenic study treatments plus an additional 90 days (spermatogenesis cycle). In addition, male subjects must refrain from donating sperm during this period and the female subjects who is eligible to participate if she is not a woman of childbearing potential (WOCBP).
  • Capable of giving signed informed consent

Exclusion Criteria

  • History of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study treatment; or interfering with the interpretation of data.
  • History of clinically significant psychiatric disorders as judged by the investigator. Psychiatric disorder requiring pharmacologic treatment in the last 5 years.
  • Any positive (abnormal) response confirmed by the investigator on a screening clinician (or qualified designee) administered Columbia Suicide Severity Rating Scale (CSSRS).
  • History or current evidence of febrile seizures, epilepsy, convulsions, significant head injury, or other significant neurologic conditions.
  • History of GI surgery (with exception of appendectomy).
  • History of Cholecystectomy
  • Any history of GI ulceration (esophageal, stomach, duodenal).
  • Any history of GI symptoms requiring treatment in the last 3 months
  • History of unexplained vaginal bleeding, endometrial hyperplasia with atypia or endometrial carcinoma
  • Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hayfever, is allowed unless it is active.
  • ALT >1.5x upper limit of normal (ULN).
  • Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 100 beats per minute [bpm]), PR interval ( 220 millisecond [msec]), QRS duration ( 120 msec), QT interval by Fridericia's correction formula (QTcF) interval (>450 msec) for male subjects and heart rate of 100 bpm for female subjects.
  • Evidence of previous myocardial infarction (does not include ST segment changes associated with re-polarization).
  • Any conduction abnormality (including but not specific to left or right complete bundle branch block, atrioventricular (AV) block [2nd degree or higher], Wolf Parkinson- White [WPW] syndrome).
  • Sinus Pauses >3 seconds
  • Any significant arrhythmia which, in the opinion of the Investigator OR GlaxoSmithKline (GSK)/ViiV Medical monitor, will interfere with the safety for the individual subject.
  • Non-sustained or sustained ventricular tachycardia (with consecutive ventricular ectopic beats).
  • Prior or concomitant therapy, where past or intended use of over-the-counter or prescription medication, including herbal medications within 7 days (or 14 days if the drug is a potential enzyme inducer), or 5 half-lives (whichever is longer) prior to dosing (paracetamol/acetaminophen [up to 2 grams per day], and 2.5%, hydrocortisone [for ECG lead contact dermatitis] is permitted any time during the study).
  • Prior or concurrent clinical study experience where, participation in the study would result in loss of blood or blood products in excess of 500 mL within a 56 day period; therefore donation or loss of greater than 400 mL of blood within the previous 3 months.
  • C
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03575962). 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.

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