Treatment of human immunodeficiency virus-1 (HIV-1) MedDRA version: 20.1 Level: PT Classification code 10020161 Term: HIV infection System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Product Name: GSK3640254 Mesylate Salt Capsule
Pharmaceutical Form: Capsule
INN or Proposed INN: GSK3640254D
CAS Number: 1818867-24-1
Cu
Sponsors
ViiV Healthcare UK Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Age 1. Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent. Type of Participant and Disease Characteristics 2.Participants who are healthy (other than HIV infection) as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, laboratory tests, and cardiac monitoring. 3.Screening CD4+ T-cell count =350 cells/mm3 4.Documented HIV infection and Screening plasma HIV-1 RNA =5000 copies/mL. A single repeat of this test is allowed within a single Screening period to determine eligibility. 5.Treatment-naïve: No ARVs (in combination or monotherapy) received after the diagnosis of HIV-1 infection. Weight 6.Body weight =50.0 kg (110 lbs.) for men and =45.0 kg (99 lbs) for women and body mass index (BMI) within the range 18.5-31.0 kg/m2 (inclusive). Sex 7.Male or female: a.Male participants: A male participant with a female partner of child-bearing potential or who is breastfeeding or pregnant must agree to use contraception as detailed in Appendix 5 of this protocol during the treatment phase 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 participants must refrain from donating sperm during this period. b.Female participants: A female participant is eligible to participate if she is not pregnant (see Appendix 5 of protocol ), not breastfeeding, and not a woman of childbearing potential (WOCBP) as defined in Appendix 5 of protocol. Informed Consent 8.Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the consent form and stated in the protocol. Other 9.For participants enrolled in France: a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 34 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical Conditions 1.Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior to starting study treatment 2.Positive Hepatitis C antibody test result at screening or within 3 months prior to starting study treatment AND positive on reflex to Hepatitis C RNA •NOTE: Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled only if a confirmatory negative Hepatitis C RNA test is obtained (central lab will automatically reflex to HCV RNA on positive HCVAb) 3.Alanine aminotransferase (ALT) >2 x upper limit of normal (ULN). A single repeat of ALT is allowed within a single Screening period to determine eligibility. 4.Bilirubin >1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) 5.Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones); 6.A pre-existing condition interfering with normal gastrointestinal anatomy or motility (e.g., gastroesophageal reflux disease [GERD], gastric ulcers, gastritis), hepatic and/or renal function, that could interfere with the absorption, metabolism, and/or excretion of the study drugs or render the subject unable to take oral study treatment. 7.Any acute laboratory abnormality at screen which, in the opinion of the investigator, should preclude participation in the study of an investigational compound. 8.Any Grade 2-4 laboratory abnormality at Screen, with the exception of creatine phosphokinase (CPK) and lipid abnormalities (e.g., total cholesterol, triglycerides, etc), and ALT (described above), will exclude a participant from the study unless the investigator can provide a compelling explanation for the laboratory result(s) and has the assent of the sponsor. A single repeat of any lab abnormality is allowed within a single Screening period to determine eligibility. 9.Any pre-existing physical or psychiatric condition (including alcohol or drug abuse), which, in the opinion of the investigator (with or without psychiatric evaluation), could interfere with the participant’s ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the participant. 10.Medical history of cardiac arrhythmias or cardiac disease or a family or personal history of long QT syndrome. Prior/Concomitant Therapy 11.History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation. Prior/Concurrent Clinical Study Experience 12.The participant has participated in a clinical trial and has received an investigational product within the 30 days prior to the first dosing day in the current study. Diagnostic assessments 13.Any positive (abnormal) response confirmed by the investigator on a Screening clinician- (or qualified designee-) administered C-SSRS. 14.Any positive result for illicit drug use (e.g., cocaine
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the antiviral activity of GSK3640254 in HIV-1-infected participants during 10 days of monotherapy; Secondary Objective: •To assess the safety and tolerability of GSK3640254 when administered as monotherapy over 10 days in HIV-1 infected participants •To characterize the pharmacokinetics of GSK3640254 dosing for 10 days in HIV-1 infected patients •To explore the relationship between GSK3640254 exposure and change in plasma HIV-1 RNA •To estimate GSK3640254 accumulation following administration of GSK3640254 for 10 days in HIV-1 infected patients. •To examine dose proportionality of GSK3640254 PK parameters following dosing for 10 days ;Primary end point(s): Maximum change from baseline (Day 1) in plasma HIV-1 ribonucleic acid (RNA);Timepoint(s) of evaluation of this end point: 11 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Days 1-24; Secondary end point(s): GSK3640254 safety and tolerability parameters: adverse events(AE); post-baseline values and changes over time of clinical laboratory evaluations, vital signs, and electrocardiogram (ECG) parameters • GSK3640254 PK parameters at the following dose administration: Day 1: area under the plasma concentration time curve from zero to 24 (AUC [0-24]), maximum observed concentration (Cmax), time to maximum observed concentration (tmax), concentration at 24 hours post dose (C24), absorption lag time (tlag) Following repeat administration: Area under the curve (Area under the plasma drug concentration-time curve from pre-dose to the end of the dosing interval at steady state (AUC [0-t]), Cmax, tmax, pre-dose concentration (C0), concentration at end of dosing interval (Ct), apparent terminal phase half-life (t1/2), and apparent oral clearance (CL/F), if data permit. GSK3640254 repeat-dose PK parameters AUC(0-t), Cmax, Ct with maximum HIV-1 RNA change from baseline Accumulation: GSK3640254 PK accumulation ratios (R): repeat -dose AUC (0-t), Cmax, and Ct compared to Day 1 AUC (0-24), Cmax, C24, respectively Relationship between Day 1 AUC (0-24), Cmax, C24, and repeat-dose AUC (0-t), Cmax and Ct and GSK3640254 dose levels | — |
Countries
France, Russian Federation, South Africa, Spain, United States
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline Research & Development Ltd.
Outcome results
None listed