Effect of GSK3640254 on the Pharmacokinetics of a Combina... | NCT03984825

NCT03984825

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Portia followed by Portia co-administered with GSK3640254	Experimental	Subjects will be administered Portia (0.03 mg EE/0.15 mg LNG) once daily on Days -3 to -1 during run-in period and on Days 1 to 10 in treatment period A. Subjects will then receive Portia (0.03 mg EE/0.15 mg LNG) co-administered with GSK3640254 200 mg once daily on Days 11 to 21 in treatment period B.	Drug: GSK3640254 Drug: Portia

Interventions

Name	Type	Description	Arm Group Labels	Other Names
GSK3640254	Drug	GSK3640254 will be available as a 100 mg capsule. Subjects will be administered 200 mg GSK3640254 once daily via the oral route on Days 11 to 21.	Portia followed by Portia co-administered with GSK3640254

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Period 1: Area Under the Plasma Concentration-time Curve From Time 0 to the End of the Dosing Interval at Steady State (AUC [0-tau]) of EE	Blood samples were collected at indicated time points for the analysis of AUC (0-tau) of EE. PK parameters were calculated by standard non-compartmental analysis. The PK population included all participants who underwent plasma PK sampling and had evaluable PK parameters estimated.	Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours
Period 2: AUC (0-tau) of EE	Blood samples were collected at indicated time points for the analysis of AUC (0-tau) of EE. PK parameters were calculated by standard non-compartmental analysis.	Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 and 24 hours post dose
Period 1:AUC (0-tau) of LNG	Blood samples were collected at indicated time points for the analysis of AUC (0-tau) of LNG. PK parameters were calculated by standard non-compartmental analysis.	Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours
Period 2: AUC (0-tau) of LNG	Blood samples were collected at indicated time points for the analysis of AUC (0-tau) of LNG. PK parameters were calculated by standard non-compartmental analysis.	Day 21: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 and 24 hours post dose
Period 1: Maximum Observed Concentration (Cmax) and Plasma Concentration at the End of the Dosing Interval (Ctau) of EE	Blood samples were collected at indicated time points for the analysis of Cmax and Ctau of EE. PK parameters were calculated by standard non-compartmental analysis.	Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours

Secondary Outcomes

Measure	Description	Time Frame
Period 1: Effect of GSK3640254 on PD of EE/LNG- Serum Progesterone Level	Serum samples were collected for the analysis of progesterone concentration levels when GSK3640254 is co-administered with EE/LNG. PD concentration Population comprised of all participants who underwent plasma PD sampling and had evaluable PD assay results.	At Day 1 and Day 10

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Subject must be 18 to 50 years of age inclusive, at the time of signing the informed consent.
Subjects who are healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring (history and ECG).
Body weight >=45.0 kilograms (kg) (99 pounds [lbs]) and body mass index (BMI) within the range 18.5 to 31.0 kilograms per meter square (kg/m^2) (inclusive).
Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
Female subjects will be included.
Subject must not be pregnant or breastfeeding.
Subject is a woman of childbearing potential (WOCBP) with intact ovarian function, as determined by medical history. Subjects must use Portia for the duration of the run-in and treatment periods.
WOCBP must have been on an acceptable form of contraceptive for at least 28 days prior to start of study intervention. Acceptable forms of contraception prior to study intervention include the following: Intrauterine device or intrauterine system; Combined estrogen and progestogen oral contraceptive; Contraceptive vaginal ring; Percutaneous contraceptive patches (if used, the patch must be removed during study participation); Bilateral tubal occlusion; Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject. The documentation on male sterility can come from the site personnel's review of subject's medical records, medical examination and/or semen analysis, or medical history interview provided by her or her partner.; Sexual abstinence.
Subjects who have been on a stable regimen of an oral contraceptive for at least 3 consecutive months must be without evidence of breakthrough bleeding or spotting.
Subjects who have been taking oral contraceptives should continue their current regimen until check-in to the clinic for the run-in period. Subjects not currently taking an oral contraceptive are eligible, provided all other eligibility criteria are met.
Subjects may proceed to the treatment period provided the toxicity profile during the run-in period with Portia is acceptable in the opinion of the investigator.
Subjects must agree to use an additional method of contraception from the following list of contraceptive methods for the run-in period, treatment period, and for 28 days after the last dose of study intervention: Non hormonal Intrauterine device; Bilateral tubal occlusion; Male partner sterilization with documentation of azoospermia prior to the female subject's entry into the study, and this male is the sole partner for that subject. The documentation on male sterility can come from the site personnel's review of subject's medical records, medical examination and/or semen analysis, or medical history interview provided by her or her partner.; Sexual abstinence. For the 28 days after study exit, women may resume oral contraceptives but double barrier methods (a combination of male condom with either cervical cap, diaphragm, or sponge with spermicide) must be used in addition.
Women of childbearing potential must have a negative highly sensitive serum pregnancy test on Day -4 and Day -1.
Additional requirements for pregnancy testing during and after study intervention as outlined in protocol.
Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form and protocol.

Exclusion Criteria:

History of jaundice associated with taking oral contraceptives or with pregnancy.
History of clinically significant irregular bleeding while taking oral contraceptives.
History of past deep venous thrombosis, pulmonary embolism, stroke, transient ischemic attack, phlebitis, or migraine headaches with prolonged aura.
History of cerebrovascular or coronary artery disease.
History of retinal vascular lesions.
History of carcinoma of the breast, endometrium, or other known estrogen-dependent neoplasia.
Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
A pre-existing condition interfering with normal gastrointestinal (GI) anatomy or motility (e.g., gastroesophageal reflux disease, 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 intervention.
Any history of significant underlying psychiatric disorder, including, but not limited to, schizophrenia, bipolar disorder with or without psychotic symptoms, other psychotic disorders, or schizotypal (personality) disorder.
Any history of major depressive disorder with or without suicidal features, or anxiety disorders that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient treatment. Subjects with other conditions such as adjustment disorder or dysthymia that have required shorter term medical therapy (<6 months) without inpatient treatment and are currently well-controlled clinically or resolved may be considered for entry after discussion and agreement with the ViiV Healthcare/GlaxoSmithKline (GSK) Medical Monitor.
Any pre-existing physical or other psychiatric condition (including alcohol or drug abuse), which, in the opinion of the investigator (with or without psychiatric evaluation), could interfere with the subject's ability to comply with the dosing schedule and protocol evaluations or which might compromise the safety of the subject.
Medical history of cardiac arrhythmias, prior myocardial infarction in the past 3 months, or cardiac disease or a family or personal history of long QT syndrome.
Presence of hepatitis B surface antigen at Screening or within 3 months prior to starting study intervention.
Positive hepatitis C antibody test result at Screening or within 3 months prior to starting study intervention AND positive on reflex to hepatitis C ribonucleic acid (RNA).
Positive HIV-1 and -2 antigen/antibody immunoassay at Screening.
ALT >1.5 times upper limit of normal (ULN). A single repeat of ALT is allowed within a single screening period to determine eligibility.
Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
Any acute laboratory abnormality at Screening which, in the opinion of the investigator, should preclude participation in the study of an investigational compound.
Any Grade 2 to 4 laboratory abnormality at Screening, with the exception of creatine phosphokinase (CPK) and lipid abnormalities (e.g., total cholesterol, triglycerides, etc), and ALT (described above), will exclude a subject 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 laboratory abnormality is allowed within a single screening period to determine eligibility.
A positive test result for drugs of abuse (including marijuana), alcohol, or cotinine (indicating active current smoking) at Screening or before the first dose of study intervention.
Unable to refrain from the use of prescription or nonprescription drugs including vitamins, herbal and dietary supplements (including St John's wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study intervention and for the duration of the study (acetaminophen/paracetamol at doses of <=2 grams/day and hydrocortisone cream 1% are permitted for use any time during the study).
Treatment with any vaccine within 30 days prior to receiving study intervention.
Unwillingness to abstain from excessive consumption of any food or drink containing grapefruit and grapefruit juice, Seville oranges, blood oranges, or pomelos or their fruit juices within 7 days prior to the first dose of study intervention(s) until the end of the study.
Participation in another concurrent clinical study or prior clinical study (with the exception of imaging trials) prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Where participation in the study would result in donation of blood or blood products in excess of 500 milliliters (mL) within 56 days.
Any positive (abnormal) response confirmed by the investigator on a screening clinician- or qualified designee-administered Columbia Suicide Severity Rating Scale (C-SSRS).
Any significant arrhythmia or ECG finding (e.g., symptomatic bradycardia, non-sustained or sustained atrial arrhythmias, non-sustained or sustained ventricular tachycardia, second-degree atrioventricular block Mobitz Type II, or third-degree atrioventricular block) which, in the opinion of the investigator or ViiV Healthcare/GSK Medical Monitor, will interfere with the safety for the individual subject.
Exclusion criteria for screening ECG (a single repeat is allowed for eligibility determination): heart rate-<50 or >100 beats per minute and QTcF->450 milliseconds.
History of regular alcohol consumption within 6 months of the study defined as: an average weekly intake of >14 units. One unit is equivalent to 8 g of alcohol: a half-pint (equivalent to 240 mL) of beer, 1 glass (125 mL) of wine or 1 (25 mL) measure of spirits.
Unable to refrain from tobacco- or nicotine-containing within 3 months prior to Screening.
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.

Contacts/Locations Module

Name	Affiliation	Role
GSK Clinical Trials	ViiV Healthcare	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
GSK Investigational Site		Austin	Texas	78744	United States

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

A total of 23 participants were enrolled in the study

Arm/Group Information

ID	Title	Description
FG000	Portia Followed by Portia + GSK3640254	Participants in Run-in period received Portia (0.03 milligram [mg] EE/0.15 mg LNG) once daily (QD) on Day -3 through Day -1. Participants in Treatment Period 1 received Portia (0.3 mg EE/ 0.15 mg LNG) QD on Day 1 through Day 10. In Treatment Period 2 participants received Portia QD co-administered with GSK3640254 200 mg QD on Day 11 through Day 21. There was no washout period between two periods.

Periods

Title

Milestones

Reasons Not Completed

Run-in Period (Day -3 to -1)

Type	Comment	Milestone Data
STARTED		FG00023 subjects
COMPLETED		FG00023 subjects
NOT COMPLETED		FG0000 subjects

Treatment Period 1 (Day 1 to 10)

Type	Comment	Milestone Data
STARTED		FG00023 subjects
COMPLETED		FG00021 subjects
NOT COMPLETED		FG000

Treatment Period 2 (Day 11 to 21)

Type	Comment	Milestone Data
STARTED		FG00021 subjects
COMPLETED		FG00017 subjects
NOT COMPLETED		FG000

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Portia Followed by Portia + GSK3640254	Participants in Run-in period received Portia (0.03 milligram [mg] EE/0.15 mg LNG) once daily (QD) on Day -3 through Day -1. Participants in Treatment Period 1 received Portia (0.3 mg EE/ 0.15 mg LNG) QD on Day 1 through Day 10. In Treatment Period 2 participants received Portia QD co-administered with GSK3640254 200 mg QD on Day 11 through Day 21. There was no washout period between two periods.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Period 1: Area Under the Plasma Concentration-time Curve From Time 0 to the End of the Dosing Interval at Steady State (AUC [0-tau]) of EE

Blood samples were collected at indicated time points for the analysis of AUC (0-tau) of EE. PK parameters were calculated by standard non-compartmental analysis. The PK population included all participants who underwent plasma PK sampling and had evaluable PK parameters estimated.

PK Population.

Posted

Geometric Mean

Geometric Coefficient of Variation

Hour*picograms per milliliter

Day 10: Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 7, 12 hours and Day 11: 24 hours

ID	Title	Description
OG000	Portia (0.3 mg EE/ 0.15 mg LNG)	Participants in period 1 received Portia (0.3 mg of EE and 0.15 mg LNG) QD on Day 1 through Day 10.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Portia - Run-in Period (Day -3 to Day -1)	Participants in Run-in period received Portia (0.03 mg EE/0.15 mg LNG) QD on Day -3 through Day -1.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Transaminases increased	Investigations	MedDRA 22.0	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
GSK Response Center	ViiV Healthcare	866-435-7343		GSKClinicalSupportHD@gsk.com

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	May 10, 2019	Jul 3, 2020	Prot_000.pdf
SAP	No	Yes	No	Statistical Analysis Plan	Jan 19, 2020	Jul 3, 2020	SAP_001.pdf

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

ID	Term
D015658	HIV Infections

ID	Term
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D015229	Sexually Transmitted Diseases, Viral

Intervention Browse Module

ID	Term
C000723722	GSK3640254
D019304	Ethinyl Estradiol-Norgestrel Combination

ID	Term
D004997	Ethinyl Estradiol
D009651	Norpregnatrienes
D009650	Norpregnanes
D009654	Norsteroids

Masking Info

Units	Counts
Participants	OG00023

EG0000 affected23 at risk

EG0014 affected23 at risk

EG0021 affected21 at risk

Title	Measurements
	OG0005.109± 3.7754

Title	Measurements
	OG000-0.049± 0.2231

Title	Measurements
	OG000-0.161± 0.2891

Title	Measurements
	OG0000.9± 2.94

Title	Measurements
	OG000-0.4± 1.54

Title	Measurements
	OG0001.8± 3.77

Title	Measurements
	OG00011.5± 24.80

Title	Measurements
	OG0004.2± 10.61

Title	Measurements
	OG000-0.57± 1.638

Title	Measurements
	OG0000.52± 2.852

Title	Measurements
	OG000-0.02± 0.867

Title	Measurements
	OG0000.001± 0.0209

Title	Measurements
	OG000-3.0± 11.32

Title	Measurements
	OG0004.291± 0.9991

Title	Measurements
	OG00028.8± 2.57

Title	Measurements
	OG00018.8± 9.25

Title	Measurements
	OG000122.7± 21.78

Title	Measurements
	OG00067.75± 8.763

Title	Measurements
	OG0000.103± 0.0555

Title	Measurements
	OG0002

Title	Measurements
	OG00085.7± 9.86

Title	Measurements
	OG00071.9± 8.87