HIV InfectionsPhase 1NCT03575962
A Study to Compare the Relative Bioavailability of Two Different Formulations of GSK3640254
A Phase 1 study testing GSK3640254 bis-hydrochloride salt capsule and GSK3640254 Mesylate Salt Capsule in people with HIV Infections, run by ViiV Healthcare at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV Infections
- What is being tested?
- GSK3640254 bis-hydrochloride salt capsule and GSK3640254 Mesylate Salt Capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 18 Jun 2018to 6 Aug 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
- Conditions
- HIV Infections
- Being tested
- GSK3640254 bis-hydrochloride salt capsule, GSK3640254 Mesylate Salt Capsule
- Keywords
- 2-period, Pharmacokinetics, FTIH, GSK3640254, healthy subject, bioavailability
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GSK3640254 bis-hydrochloride salt capsuleDrug
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.
GSK3640254 Mesylate Salt CapsuleDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| GSK3640254 Bis-hydrochloride followed by GSK3640254 mesylate | Experimental | 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. Receives: Drug: GSK3640254 bis-hydrochloride salt capsule; Drug: GSK3640254 Mesylate Salt Capsule |
| GSK3640254 Mesylate followed by GSK3640254 Bis-hydrochloride | Experimental | 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. Receives: Drug: GSK3640254 bis-hydrochloride salt capsule; Drug: GSK3640254 Mesylate Salt Capsule |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Blood samples were collected at designated timepoints. Pharmacokinetic (PK) parameters of GSK3640254 were calculated using non-compartmental methods. Geometric mean and percentage (%) geometric coefficient of variation have been presented.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post-dose in each treatment period
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
Blood samples were collected at designated timepoints. PK parameters of GSK3640254 were calculated using non-compartmental methods. Geometric mean and % geometric coefficient of variation have been presented. Statistical analysis of PK parameters was done using mixed effect model for evaluation of relative bioavailability (Frel). Point estimate and 90% confidence interval (CI) for the ratio of geometric least square mean of the test mesylate salt capsule to the reference Hydrochloride capsule were calculated for AUC(0-t).
Measured: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, and 72 hours post-dose in each treatment period
Maximum Observed Concentration (Cmax) of GSK3640254 Following Single Oral Dose in Healthy Participants
Blood samples were collected at designated timepoints. PK parameters of GSK3640254 were calculated using non-compartmental methods. Geometric mean and % geometric coefficient of variation have been presented. Statistical analysis of PK parameters was done using mixed effect model for evaluation of Frel. Point estimate and 90% CI for the ratio of geometric least square mean of the test mesylate salt capsule to the reference Hydrochloride capsule were calculated for Cmax.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, and 72 hours post-dose in each treatment period
Time to Reach Maximum Observed Concentration (Tmax) of GSK3640254 Following Single Oral Dose in Healthy Participants
Blood samples were collected at designated timepoints. PK parameters of GSK3640254 were calculated using non-compartmental methods. Median and full range of Tmax have been presented.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, and 72 hours post-dose in each treatment period
Concentration at 24 Hours Post-dose (C24h) of GSK3640254 Following Single Oral Dose in Healthy Participants
Blood samples were collected at designated timepoints. PK parameters of GSK3640254 were calculated using non-compartmental methods. Geometric mean and % geometric coefficient of variation have been presented.
Measured: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose in each treatment period
Secondary outcomes (13)
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, 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 inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect and other situations according to medical or scientific judgement.
Measured: Up to 25 days
Change From Baseline in Clinical Chemistry Parameters; Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST)
Blood samples were collected to analyze the clinical chemistry parameters; ALT, ALP and AST. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the post-Dose visit value. Mean and standard deviation have been presented.
Measured: Baseline (Day -1) and Day 3
Change From Baseline in Clinical Chemistry Parameters; Bicarbonate, Calcium, Chloride, Glucose (Fasting), Potassium, Sodium and Urea
Blood samples were collected to analyze the clinical chemistry parameters; Bicarbonate, Calcium, Chloride, Glucose (fasting), Potassium, Sodium and Urea. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the post-Dose visit value. Mean and standard deviation have been presented.
Measured: Baseline (Day -1) and Day 3
Change From Baseline in Clinical Chemistry Parameters; Bilirubin, Creatinine and Direct Bilirubin
Blood samples were collected to analyze the clinical chemistry parameters; Bilirubin, Creatinine and Direct Bilirubin. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the post-Dose visit value. Mean and standard deviation have been presented.
Measured: Baseline (Day -1) and Day 3
Change From Baseline in Clinical Chemistry Parameter; Protein
Blood samples were collected to analyze the clinical chemistry parameter; Protein. Day-1 was considered as Baseline. Change from Baseline was calculated by subtracting Baseline value from the post-Dose visit value. Mean and standard deviation have been presented.
Measured: Baseline (Day -1) and Day 3
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Blood samples were collected to analyze the hematology parameters; Hematocrit (Hct), Hemoglobin (Hb), Leukocytes, Lymphocytes, Neutrophils and Platelets. PCI ranges were Hct (Male and Female [high: >0.54 proportion of red blood cells in blood]), Hb (Male and Female [high: >180 grams per liter]), lymphocytes (low: <0.8x10^9 cells per liter), neutrophils (low: <1.5x10^9 cells per liter), platelets (low: <100x10^9 cells per liter and high: >550x10^9 cells per liter) and leukocytes (low: <3x10^9 cells per liter and high: >12x10^9 cells per liter). Participants were counted in the worst case category such that their value changed to (low, normal or high). If values were unchanged (example: High to High), or whose value became normal, were recorded in the 'To Normal or No Change' category.
Measured: Up to 22 days
Number of Participants With Urinalysis Results by Dipstick Method by Visit
Urine samples were collected to assess urine bilirubin, urine glucose, urine ketones, urine leukocyte esterase (LE), urine nitrite, urine occult blood, urine protein, urobilinogen and monitor urine potential of hydrogen (pH). The dipstick test gave results in a semi-quantitative manner, and results for urinalysis parameters were recorded as negative, trace and positive, indicating proportional concentrations in the urine sample. All the numeric result values >0 have been considered as "positive".
Measured: Day -1 and Day 3
Number of Participants With Clinically Significant Abnormal Findings for Electrocardiogram (ECG) Parameters
A single 12-lead ECGs was obtained using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, QT corrected (QTc) and QT interval corrected for heart rate according to Fridericia's formula (QTcF) intervals. Clinically significant abnormal ranges were: PR: lower: <120 milliseconds (msec) and upper: >200 msec; QRS: lower: <60 msec and upper: >120 msec and QTcF: lower: <320 msec and upper: >450 msec. The number of participants with clinically significant abnormal findings for ECG parameters have been presented.
Measured: Day -1, pre-dose, 2, 4, 6, 24 and 72 hours post-dose in each treatment period
Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) at Indicated Time-points
Vital signs including DBP and SBP were measured at the indicated time-points and summarized during the study to evaluate the safety of the participants. Mean and standard deviation have been presented.
Measured: Day -1, pre-dose, 2, 4, 6, 24 and 72 hours post-dose in each treatment period
Pulse Rate (PR) at Indicated Time-points
Vital sign including PR was measured at the indicated time-points and summarized during the study to evaluate the safety of the participants. Mean and standard deviation have been presented.
Measured: Day -1, pre-dose, 2, 4, 6, 24 and 72 hours post-dose in each treatment period
Respiratory Rate (RR) at Indicated Time-points
Vital sign including RR was measured at the indicated time-point and summarized during the study to evaluate the safety of the participants. Mean and standard deviation have been presented.
Measured: Day -1, pre-dose, 2, 4, 6, 24 and 72 hours post-dose in each treatment period
Temperature at Indicated Time-points
Vital sign including temperature was measured at the indicated time-points and summarized during the study to evaluate the safety of the participants. Mean and standard deviation have been presented.
Measured: Day -1, pre-dose, 2, 4, 6, 24 and 72 hours post-dose in each treatment period
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)
Assessment of suicidality was conducted using the C-SSRS, a brief questionaire designed to assess severity and change in suicidality by integrating both behavior and ideation using a semi-structured interview to probe participant responses.
Measured: Day 3 in each treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2018
- Study start18 Jun 2018
- Primary completion6 Aug 2018
- Study completion6 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by ViiV HealthcareThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- 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)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- ViiV Healthcare
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, ViiV Healthcare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03575962
- Sponsor's protocol ID
- 208131
- Other IDs
- 2018-001175-21, 2018
- Status last verified
- Jul 2019
- First submitted
- 12 Jun 2018
- Last updated
- 6 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Publications
Joshi SR, Fernando D, Igwe S, McKenzie L, Krishnatry AS, Halliday F, Zhan J, Greene TJ, Xu J, Ferron-Brady G, Lataillade M, Min S. Phase I evaluation of the safety, tolerability, and pharmacokinetics of GSK3640254, a next-generation HIV-1 maturation inhibitor. Pharmacol Res Perspect. 2020 Dec;8(6):e00671. doi: 10.1002/prp2.671.
PubMed 33200887
Study at a glance
From the registry record, last updated by the sponsor on 6 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03575962
- Acronym / sponsor ID
- 208131
- Conditions
- HIV Infections
- Keywords
- 2-period, Pharmacokinetics, FTIH, GSK3640254, healthy subject, bioavailability
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- ViiV HealthcareIndustry (pharma, biotech, devices)
- Study start
- 18 Jun 2018 (actual)
- Primary completion
- 6 Aug 2018 (actual)
- Study completion
- 6 Aug 2018 (actual)
- First posted
- 3 Jul 2018 (actual)
- Results
- Posted 6 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Subjects will receive GSK3640254 bis-hydrochloride salt capsule followed by mesylate salt capsule or vice versa in two treatment periods.
| Arm | Type | Receives |
|---|---|---|
| GSK3640254 Bis-hydrochloride followed by GSK3640254 mesylate | Experimental | Drug: GSK3640254 bis-hydrochloride salt capsule, Drug: GSK3640254 Mesylate Salt CapsuleThe 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. |
| GSK3640254 Mesylate followed by GSK3640254 Bis-hydrochloride | Experimental | Drug: GSK3640254 bis-hydrochloride salt capsule, Drug: GSK3640254 Mesylate Salt CapsuleThe 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. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (34 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GSK3640254 bis-hydrochloride salt capsuleAdministered 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 Bis-hydrochloride followed by GSK3640254 mesylate, GSK3640254 Mesylate followed by GSK3640254 Bis-hydrochloride |
| GSK3640254 Mesylate Salt CapsuleAdministered 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 Bis-hydrochloride followed by GSK3640254 mesylate, GSK3640254 Mesylate followed by GSK3640254 Bis-hydrochloride |
Primary outcome
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
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post-dose in each treatment period
Blood samples were collected at designated timepoints. Pharmacokinetic (PK) parameters of GSK3640254 were calculated using non-compartmental methods. Geometric mean and percentage (%) geometric coefficient of variation have been presented.
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
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, and 72 hours post-dose in each treatment period
Blood samples were collected at designated timepoints. PK parameters of GSK3640254 were calculated using non-compartmental methods. Geometric mean and % geometric coefficient of variation have been presented. Statistical analysis of PK parameters was done using mixed effect model for evaluation of relative bioavailability (Frel). Point estimate and 90% confidence interval (CI) for the ratio of geometric least square mean of the test mesylate salt capsule to the reference Hydrochloride capsule were calculated for AUC(0-t).
Maximum Observed Concentration (Cmax) of GSK3640254 Following Single Oral Dose in Healthy Participants
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, and 72 hours post-dose in each treatment period
Blood samples were collected at designated timepoints. PK parameters of GSK3640254 were calculated using non-compartmental methods. Geometric mean and % geometric coefficient of variation have been presented. Statistical analysis of PK parameters was done using mixed effect model for evaluation of Frel. Point estimate and 90% CI for the ratio of geometric least square mean of the test mesylate salt capsule to the reference Hydrochloride capsule were calculated for Cmax.
Time to Reach Maximum Observed Concentration (Tmax) of GSK3640254 Following Single Oral Dose in Healthy Participants
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, and 72 hours post-dose in each treatment period
Blood samples were collected at designated timepoints. PK parameters of GSK3640254 were calculated using non-compartmental methods. Median and full range of Tmax have been presented.
Concentration at 24 Hours Post-dose (C24h) of GSK3640254 Following Single Oral Dose in Healthy Participants
Time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12 and 24 hours post-dose in each treatment period
Blood samples were collected at designated timepoints. PK parameters of GSK3640254 were calculated using non-compartmental methods. Geometric mean and % geometric coefficient of variation have been presented.
13 secondary outcomes
Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
Time frame: Up to 25 days
Change From Baseline in Clinical Chemistry Parameters; Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST)
Time frame: Baseline (Day -1) and Day 3
Change From Baseline in Clinical Chemistry Parameters; Bicarbonate, Calcium, Chloride, Glucose (Fasting), Potassium, Sodium and Urea
Time frame: Baseline (Day -1) and Day 3
Change From Baseline in Clinical Chemistry Parameters; Bilirubin, Creatinine and Direct Bilirubin
Time frame: Baseline (Day -1) and Day 3
Change From Baseline in Clinical Chemistry Parameter; Protein
Time frame: Baseline (Day -1) and Day 3
Number of Participants With Worst Case Hematology Results by Potential Clinical Importance (PCI) Criteria
Time frame: Up to 22 days
Number of Participants With Urinalysis Results by Dipstick Method by Visit
Time frame: Day -1 and Day 3
Number of Participants With Clinically Significant Abnormal Findings for Electrocardiogram (ECG) Parameters
Time frame: Day -1, pre-dose, 2, 4, 6, 24 and 72 hours post-dose in each treatment period
Diastolic Blood Pressure (DBP) and Systolic Blood Pressure (SBP) at Indicated Time-points
Time frame: Day -1, pre-dose, 2, 4, 6, 24 and 72 hours post-dose in each treatment period
Pulse Rate (PR) at Indicated Time-points
Time frame: Day -1, pre-dose, 2, 4, 6, 24 and 72 hours post-dose in each treatment period
Respiratory Rate (RR) at Indicated Time-points
Time frame: Day -1, pre-dose, 2, 4, 6, 24 and 72 hours post-dose in each treatment period
Temperature at Indicated Time-points
Time frame: Day -1, pre-dose, 2, 4, 6, 24 and 72 hours post-dose in each treatment period
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)
Time frame: Day 3 in each treatment period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33200887Joshi SR, Fernando D, Igwe S, McKenzie L, Krishnatry AS, Halliday F, Zhan J, Greene TJ, Xu J, Ferron-Brady G, Lataillade M, Min S. Phase I evaluation of the safety, tolerability, and pharmacokinetics of GSK3640254, a next-generation HIV-1 maturation inhibitor. Pharmacol Res Perspect. 2020 Dec;8(6):e00671. doi: 10.1002/prp2.671.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
ViiV Healthcare
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GSK3640254 bis-hydrochloride salt capsule and GSK3640254 Mesylate Salt Capsule in people with HIV Infections, run by ViiV Healthcare at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Pre-dose, 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48 and 72 hours post-dose in each treatment period). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03575962, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Sep 2019.