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

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ClinicalTrials.gov Identifier: NCT03575962
Recruitment Status : Recruiting
First Posted : July 3, 2018
Last Update Posted : July 3, 2018
Sponsor:
Information provided by (Responsible Party):
ViiV Healthcare

Brief 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.

Condition or disease Intervention/treatment Phase
HIV Infections Drug: GSK3640254 bis-hydrochloride salt capsule Drug: GSK3640254 Mesylate Salt Capsule Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Subjects will receive GSK3640254 bis-hydrochloride salt capsule followed by mesylate salt capsule or vice versa in two treatment periods.
Masking: None (Open Label)
Masking Description: This is an open-label study.
Primary Purpose: Treatment
Official Title: A Single Centre, 2-period, Randomized, Open-label Phase 1 Study to Assess the Relative Bioavailability of a Mesylate Salt Capsule of GSK3640254 Compared to a Hydrochloride Salt Capsule in Healthy Participants
Actual Study Start Date : June 19, 2018
Estimated Primary Completion Date : July 14, 2018
Estimated Study Completion Date : July 14, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS Sodium

Arm Intervention/treatment
Experimental: GSK3640254 Bis-hydrochloride followed by GSK3640254 mesylate
The subjects in this arm will receive an oral administration of 200 mg, as 2 GSK3640254 bis-hydrochloride salt Capsules(reference), as single oral dose, on the morning of Day 1 during Period 1 of the study. This will be followed by an oral administration of 200 mg, as 2 GSK3640254 Mesylate salt capsule (test), as single oral dose, on the morning of Day 1, during Period 2 of the study. The drug will be administered following a moderate calorie and fat meal. There will be a minimum washout of 7 days between each dose of study treatment.
Drug: GSK3640254 bis-hydrochloride salt capsule
Administered orally (as single dose) on morning of Day 1, as 2 capsules of 100 mg following a moderate calorie and fat meal during Period 1 and Period 2, at the specified sequence, as per study.

Drug: GSK3640254 Mesylate Salt Capsule
Administered orally (as single dose) on morning of Day 1, as 2 capsules of , 100 mg following a moderate calorie and fat meal during Period 1 and Period 2, at the specified sequence, as per study.

Experimental: GSK3640254 Mesylate followed by GSK3640254 Bis-hydrochloride
The subjects in this arm will receive an oral administration of 200 mg as 2 GSK3640254 Mesylate salt capsule (test), as single oral dose, on the morning of Day 1 during Period 1 of the study. This will be followed by an oral administration of 200 mg, as 2 GSK3640254 bis-hydrochloride salt Capsule, 100 mg (reference), as single oral dose, on the morning of Day 1 during Period 2, of the study. The drug, will be administered following a moderate calorie and fat meal. There will be a minimum washout of 7 days between each dose of study treatment.
Drug: GSK3640254 bis-hydrochloride salt capsule
Administered orally (as single dose) on morning of Day 1, as 2 capsules of 100 mg following a moderate calorie and fat meal during Period 1 and Period 2, at the specified sequence, as per study.

Drug: GSK3640254 Mesylate Salt Capsule
Administered orally (as single dose) on morning of Day 1, as 2 capsules of , 100 mg following a moderate calorie and fat meal during Period 1 and Period 2, at the specified sequence, as per study.




Primary Outcome Measures :
  1. Area under the plasma concentration-time curve (AUC) from time of dose extrapolated to infinity (AUC [0-inf] ) for GSK3640254 bishydrochloride salt capsule [ Time Frame: Pre-dose, 0.5 hour, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 hour post-dose during each Period. ]
    Serial blood samples, of approximately 2 milliliter (mL), will be collected for measurement of plasma concentrations of GSK3640254 bishydrochloride salt.

  2. AUC from time 0 to time of last quantifiable concentration (tlast), AUC (0-tlast), for GSK3640254 bishydrochloride salt capsule [ Time Frame: Pre-dose, 0.5 hour, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 hour post-dose during each Period. ]
    Serial blood samples, of approximately 2 mL, will be collected for measurement of plasma concentrations of GSK3640254 bishydrochloride salt.

  3. Maximum observed concentration (Cmax) for GSK3640254 bishydrochloride salt capsule [ Time Frame: Pre-dose, 0.5 hour, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 hour post-dose during each Period. ]
    Serial blood samples, of approximately 2 mL, will be collected for measurement of plasma concentrations ofGSK3640254 bishydrochloride salt.

  4. Time to Cmax (Tmax) for GSK3640254 bishydrochloride salt capsule [ Time Frame: Pre-dose, 0.5 hour, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 hour post-dose during each Period. ]
    Serial blood samples, of approximately 2 mL, will be collected for measurement of plasma concentrations ofGSK3640254 bishydrochloride salt.

  5. Concentration at 24 hours post dose (C24hour), for GSK3640254 bishydrochloride salt capsule [ Time Frame: Pre-dose, 0.5 hour, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 hour post-dose during each Period. ]
    Serial blood samples, of approximately 2 mL, will be collected for measurement of plasma concentrations ofGSK3640254 bishydrochloride salt.

  6. Relative bioavailability (Frel), based on AUC for GSK3640254 bishydrochloride salt capsule [ Time Frame: Pre-dose, 0.5 hour, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 hour post-dose during each Period. ]
    Serial blood samples, of approximately 2 mL, will be collected for measurement of plasma concentrations of GSK3640254 bishydrochloride salt.

  7. Frel based on Cmax, for GSK3640254 bishydrochloride salt capsule [ Time Frame: Pre-dose, 0.5 hour, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 hour post-dose during each Period. ]
    Serial blood samples, of approximately 2 mL, will be collected for measurement of plasma concentrations of GSK3640254 bishydrochloride salt.

  8. AUC (0-inf) for GSK3640254 mesylate salt capsule [ Time Frame: Pre-dose, 0.5 hour, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 hour post-dose during each Period. ]
    Serial blood samples, of approximately 2 mL, will be collected for measurement of plasma concentrations of GSK3640254 mesylate salt.

  9. AUC (0-tlast) for GSK3640254 mesylate salt capsule [ Time Frame: Pre-dose, 0.5 hour, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 hour post-dose during each Period. ]
    Serial blood samples, of approximately 2 mL, will be collected for measurement of plasma concentrations of GSK3640254 mesylate salt.

  10. Cmax for GSK3640254 mesylate salt capsule [ Time Frame: Pre-dose, 0.5 hour, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 hour post-dose during each Period. ]
    Serial blood samples, of approximately 2 mL, will be collected for measurement of plasma concentrations of GSK3640254 mesylate salt.

  11. Tmax for GSK3640254 mesylate salt capsule [ Time Frame: Pre-dose, 0.5 hour, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 hour post-dose during each Period. ]
    Serial blood samples, of approximately 2 mL, will be collected for measurement of plasma concentrations of GSK3640254 mesylate salt.

  12. C24hour for GSK3640254 mesylate salt capsule [ Time Frame: Pre-dose, 0.5 hour, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 hour post-dose during each Period. ]
    Serial blood samples, of approximately 2 mL, will be collected for measurement of plasma concentrations of GSK3640254 mesylate salt.

  13. Frel based on AUC, for GSK3640254 mesylate salt capsule [ Time Frame: Pre-dose, 0.5 hour, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 hour post-dose during each Period. ]
    Serial blood samples, of approximately 2 mL, will be collected for measurement of plasma concentrations of GSK3640254 mesylate salt

  14. Frel based on Cmax, for GSK3640254 mesylate salt capsule [ Time Frame: Pre-dose, 0.5 hour, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 hour post-dose during each Period. ]
    Serial blood samples, of approximately 2 mL, will be collected for measurement of plasma concentrations of GSK3640254 mesylate salt


Secondary Outcome Measures :
  1. Number of subjects with adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 25 days ]
    An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, is a congenital anomaly/ birth defect and other situations which involve medical or scientific judgment.

  2. Number of subjects with electrocardiogram (ECG) parameters of potential clinical importance (PCI) [ Time Frame: Up to 25 days ]
    Twelve-lead ECGs will be performed with the subject, at specified timepoints during the study, using an automated ECG machine.

  3. Number of subjects with vitals signs of PCI [ Time Frame: Up to 25 days ]
    The number of subjects with vital signs of PCI, for systolic blood pressure (SBP), diastolic blood pressure (DBP), temperature, respiratory rate and heart rate. Vitals will be measured in a semi-supine position, after 5 minutes rest at specific time points, during the study.

  4. Number of subjects with hematology values of PCI [ Time Frame: Up to 25 days ]
    Blood samples will be collected to measure platelets, red blood cell (RBC) count, reticulocytes, hemoglobin, hematocrit, RBC indices, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), basophils, eosinophils, lymphocytes, monocytes and neutrophils

  5. Number of subjects with clinical chemistry values of PCI [ Time Frame: Up to 25 days ]
    Blood samples will be collected to measure blood urea nitrogen (BUN), creatinine, fasting glucose, bicarbonate, sodium, potassium, chloride, Total carbon dioxide (CO2), phosphorous, calcium, Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase, Creatine kinase (CK), total and direct bilirubin, and total protein.

  6. Number of subjects with urinalysis values of PCI [ Time Frame: Up to 25 days ]
    Urine samples will be collected to measure specific gravity, potential of hydrogen (pH), glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, and leukocytes by dipstick method at specified time points.

  7. Columbia Suicide Severity Rating scale- as safety biomarker [ Time Frame: Day 3 ]
    C-SSRS is interview that captures occurrence, severity, and frequency of suicide-related thoughts and behavior. A clinician-rated scale which will evaluate severity and change of suicidality by integrating both suicidal behaviour (SB) and ideation (SI). For SB scale, subjects were scored as "non-suicidal" (00), "preparatory acts or behaviour communicating ideation" (01), "aborted attempt" (02), "interrupted attempt" (03) or "actual attempt" (04) based on most severe score (4 being the most severe). On SI scale, subjects were scored as "non-suicidal" (00), "wish to be dead" (01), "non-specific active suicidal thoughts" (02), "active suicidal ideation with associated thoughts of methods without intent" (03), "active suicidal ideation with some intent to act on suicidal thoughts without clear plan" (04), "active suicidal ideation with plan and intent" (05), based on the most severe score (5 being most severe). 0 indicated absence of symptom and higher score indicated greater severity.



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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 <35% of total).
  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome).
  • Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome.
  • ECG, screening details where heart rate (<40 or >100 beats per minute [bpm]), PR interval (<120 or >220 millisecond [msec]), QRS duration (<70 or >120 msec), QT interval by Fridericia's correction formula (QTcF) interval (>450 msec) for male subjects and heart rate of <50 or >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.
  • Current enrollment or past participation within the last 3 months before signing of consent in this or any other clinical study involving an investigational study treatment or any other type of medical research.
  • Subjects, who have previously been enrolled in this study.
  • Presence of Hepatitis B surface antigen (HBsAg) at screening or positive Hepatitis C antibody test result at screening or within 3 months prior to first dose.
  • Confirmed positive pre-study drug/alcohol screen.
  • Positive human immunodeficiency virus (HIV) antibody test.
  • Regular use of known drugs of abuse, or history of drug or alcohol abuse in the past 5 years.
  • Regular alcohol consumption within 6 months prior to the study defined as an average weekly intake of >21 units for males or >14 units for females. One unit is equivalent to 8 gram of alcohol: a half-pint (approximately 240 mL) of beer or 1 (25 mL) measure of spirits. One glass (125 mL) of wine is equivalent to 1.5 to 2 units, depending on type)
  • Current use or history of regular use of tobacco- or nicotine-containing products within 6 months prior to screening. A confirmed carbon monoxide breath test reading of greater than 10 parts per million.
  • Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates participation in the study.
  • Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening.
  • Subjects who do not have the ability to swallow size 00 capsules.
  • Subjects who are study site employees, or immediate family members of a study site or sponsor employee.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03575962


Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

Locations
United Kingdom
GSK Investigational Site Recruiting
Nottingham, United Kingdom, NG11 6JS
Contact: US GSK Clinical Trials Call Center    877-379-3718    GSKClinicalSupportHD@gsk.com   
Contact: EU GSK Clinical Trials Call Center    +44 (0) 20 8990 4466    GSKClinicalSupportHD@gsk.com   
Sponsors and Collaborators
ViiV Healthcare
Investigators
Study Director: GSK Clinical Trials ViiV Healthcare

Responsible Party: ViiV Healthcare
ClinicalTrials.gov Identifier: NCT03575962     History of Changes
Other Study ID Numbers: 208131
First Posted: July 3, 2018    Key Record Dates
Last Update Posted: July 3, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available, within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided, after a research proposal is submitted and has submitted 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.
URL: http://clinicalstudydatarequest.com

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by ViiV Healthcare:
2-period
Pharmacokinetics
FTIH
GSK3640254
healthy subject
bioavailability

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases