ING200336, Pharmacokinetic and Safety Study in Pregnant Women With Human Immuno Virus Infection
Study Details
Study Description
Brief Summary
In this study, the dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) fixed dose combination (FDC) tablet is being made available to women who become pregnant while participating in study ING117172. Continuation of antiretroviral therapy (ART) is key to both mother and the unborn fetus in order to maintain virologic suppression in the mother (thereby decreasing the risk for maternal disease progression), but also to reduce the risk of maternal-fetal transmission of human immunodeficiency virus type 1 (HIV-1) to her unborn child. This study also offers the first opportunity to investigate the impact of pregnancy on DTG pharmacokinetics (PK). This is an open-label, single arm interventional study. The number of women that will be enrolled into this study cannot be established a priori, as unintended pregnancies cannot be determined in advance. The maximum number of women would include all of those women randomized to DTG/ABC/3TC FDC (approximately 237), though unintended pregnancies in all of these women would not be anticipated.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: DTG/ABC/3TC All subjects will be administered DTG 50 milligrams (mg)/ABC 600 mg/3TC 300 mg FDC tablet once daily, with or without food. |
Drug: DTG 50 mg /ABC 600 mg /3TC 300 mg FDC tablets
The DTG 50 mg /ABC 600 mg /3TC 300 mg FDC tablet is a purple, oval, biconvex tablets. The tablet contains 52.6 mg DTG sodium which is equivalent to 50 mg DTG free acid, 702 mg ABC sulphate which is equivalent to 600 mg ABC and 300 mg 3TC.
|
Outcome Measures
Primary Outcome Measures
- Area Under the Plasma Concentration Time Curve at Steady State During a Dosing Interval (AUC [0-tau]) for Dolutegravir [Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum]
Blood samples were collected at indicated timepoints for Pharmacokinetic (PK) analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
- Maximum Observed Plasma Concentration (Cmax) for Dolutegravir [Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum]
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
- Drug Concentration at the End of Dosing Interval (Ctau) for Dolutegravir [24 hours post dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum]
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
- Apparent Oral Clearance (CL/F) for Dolutegravir [Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum]
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
- Steady State Volume of Distribution (Vss/F) After Extravascular Administration for Dolutegravir [Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum]
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
- Half-life (T1/2) for Dolutegravir [Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum]
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
- Number of Participants (Pregnant Women) With Maximum Severity of Post-Baseline Emergent Hematology Toxicities: Hemoglobin [Up to Week 32 of study]
Blood samples were collected for analysis of hemoglobin. Any abnormality was graded according to Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). Number of participants (Pregnant Women) with maximum severity of post-Baseline emergent toxicities with respect to hemoglobin has been presented.
- Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) [At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study]
Blood samples were collected for the analysis of chemistry parameters including ALT and AST.
- Change From Baseline in Chemistry Parameters: ALT and AST [Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study]
Blood samples were collected for the analysis of chemistry parameters including ALT and AST. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
- Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine [At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study]
Blood samples were collected for the analysis of chemistry parameters including Bilirubin and Creatinine.
- Change From Baseline in Chemistry Parameters: Bilirubin and Creatinine [Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study]
Blood samples were collected for the analysis of chemistry parameters including Bilirubin and Creatinine. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
- Absolute Values of the Hematology Parameters: Hemoglobin [At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study]
Blood samples were collected for the analysis of hematology parameters including hemoglobin.
- Change From Baseline in Hematology Parameters: Hemoglobin [Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study]
Blood samples were collected for the analysis of hematology parameters including hemoglobin. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
- Absolute Values of the Hematology Parameters: Leukocytes and Platelets [At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study]
Blood samples were collected for the analysis of hematology parameters including leukocytes and platelets.
- Change From Baseline in Hematology Parameters: Leukocytes and Platelets [Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study]
Blood samples were collected for the analysis of hematology parameters including leukocytes and platelets. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
- Number of Participants (Pregnant Women) Who Discontinued the Treatment Due to Adverse Events (AE) [Up to Week 292]
An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study treatment. Number of participants (pregnant women) who discontinued the treatment due to adverse events have been presented.
- Number of Participants (Pregnant Women) Demonstrated Congenital Malformations [At delivery (up to Week 40 of pregnancy)]
Data for participants (pregnant women) demonstrated congenital malformations was reported.
- Number of Participants (Pregnant Women) With Adverse Events (AE) as Per Severity Grades [Up to 292 Weeks]
Number of participants (pregnant women) with adverse events (AE) as per severity grades were presented. Grade 1 is mild, grade 2 is moderate, grade 3 is severe or medically significant but not immediately life-threatening and grade 4 is life-threatening consequences; urgent intervention required.
Secondary Outcome Measures
- Time to Cmax (Tmax) for Dolutegravir [Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum]
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
- Pre-dose Plasma Concentration (C0) for Dolutegravir [Pre-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum]
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
- Unbound DTG Concentrations in Plasma at 3 and 24 Hours Post Dose of Dolutegravir [At 3 hours and 24 hours post dose in Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum]
Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum.
- Total DTG Concentrations in Plasma From Cord Blood and Maternal Blood at the Time of Delivery [At delivery (up to Week 40 of pregnancy)]
Blood samples were collected at the time of delivery for PK analysis of dolutegravir.
- Number of Participants (Pregnant Women) With Treatment-emergent Genotypic and/or Phenotypic Resistance Who Met Confirmed Virologic Withdrawal Criteria [Up to Week 32 of study]
Number of participants (pregnant women) with treatment-emergent genotypic and/or phenotypic resistance who met confirmed virologic withdrawal criteria are presented. Genotypic and phenotypic analyses were carried out by Monogram Biosciences using, but not limited to, their Standard Phenosense and GenoSure testing methods for protease (PRO) and reverse transcriptase (RT), or with their GeneSeq Integrase and PhenoSense Integrase assays.
- Number of Participants (Pregnant Women) With Live Birth Outcome Categories [At delivery (up to Week 40 of pregnancy)]
Participants (pregnant women) with following live birth outcome categories are reported- Vaginal Birth, Planned Caesarean Section, Unscheduled Caesarean Section and Preterm Delivery.
- Gestational Age of Infants [At birth]
Gestational age is defined as the number of weeks between the first day of the mother's last normal menstrual period and the day of birth. Data for gestational age of infants has been presented.
- Neonatal Length and Head Circumference at Birth [At birth]
Data for neonatal length and head circumference at birth are reported.
- Neonatal Weight at Birth [At birth]
Data for neonatal weight at birth has been reported.
- Number of Infants by Their Weight Categories at Birth [At birth]
Weight of infants at birth were categorized as: Small for Gestational Age (SGA) defined neonates under the 10th percentile in weight, Appropriate for Gestational Age (AGA) characterized neonates between the 10th and 90th percentiles in weight and Large for Gestational Age (LGA) referred to neonates over the 90th percentile in weight.
- Number of Infants by Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) Score at 1 and 5 Minutes After Birth [1 and 5 minutes after birth]
APGAR is a quick test to assess the health of new born. The test is performed at 1 and 5 minutes after birth. APGAR scale is determined by evaluating the new born on five categories (appearance, pulse, grimace, activity and respiration) on a scale from zero to two with 2 being the best score, then summing up the values obtained from all five categories. APGAR score ranges from 0 to 10 (Higher score indicates better health) where a score of 7 and above is normal. Number of infants by APGAR score at 1 and 5 minutes after birth are presented.
- Percentage of Participants (Pregnant Women) With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) by Visit [At Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 and Week 32 of study]
Percentage of participants (pregnant women) with plasma HIV-1 RNA <50 c/mL are presented. Plasma samples were collected for quantitative analysis of HIV-1 RNA.
- Percentage of Participants (Pregnant Women) With Plasma HIV-1 RNA <400 c/mL by Visit [At Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 and Week 32 of study]
Percentage of participants (pregnant women) with plasma HIV-1 RNA <400 c/mL are presented. Plasma samples were collected for quantitative analysis of HIV-1 RNA.
- Absolute Values of Cluster of Differentiation 4 (CD4+) T Cell Counts by Visit [At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 and Week 32 of study]
Blood samples were collected for the analysis of CD4+ T cell counts using cytometry.
- Change From Baseline in CD4+ T Cell Counts by Visit [Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 and Week 32 of study]
Blood samples were collected for the analysis of CD4+ T cell counts using cytometry. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value.
- Number of Participants (Pregnant Women) With Disease Progression [Up to Week 32 of study]
Disease progression included HIV-associated conditions, acquired immunodeficiency syndrome (AIDS) and death. Number of participants (pregnant women) with disease progression to Centers for Disease Control and Prevention (CDC) class C or death have been presented.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
HIV infected females participating in ING117172 on the DTG/ABC/3TC treatment arm who became pregnant with a singleton and have not met any safety or confirmed virologic withdrawal criteria.
-
Signed and dated written informed consent is obtained from the subject or the subject's legal representative prior to screening.
-
Willingness and intent to continue pregnancy
-
Willingness to continue to receive DTG/ABC/3TC FDC.
-
Willingness to enter the Antiretroviral Pregnancy Registry.
-
Willingness to share medical information about herself and her infant for collection of delivery and infant outcomes as it relates to this study.
-
Subjects enrolled in France: a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Exclusion Criteria:
-
History of allergy/sensitivity to DTG, ABC and/or 3TC.
-
History of severe pre-clampsia, eclampsia, or hemolysis, elevated liver enzymes and low platelet count (HELLP)
-
Any evidence of an active Center for Disease Control and Prevention (CDC) Category C disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy or historic or current CD4+ cell levels <200 cells/millimeter^3.
-
Subjects with any degree of hepatic impairment.
-
Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia; other localized malignancies require agreement between the investigator and the Study medical monitor for inclusion of the subject.
-
Subjects who in the investigator's judgment, poses a significant suicidality risk. Recent history of suicidal behavior and/or suicidal ideation may be considered as evidence of serious suicide risk.
-
Subjects with evidence of ongoing hepatitis B infection at screening, or anticipated need for Hepatitis C Virus therapy during the study.
-
Treatment with any of the following agents within 28 days of Baseline: radiation therapy; cytotoxic chemotherapeutic agents; any immunomodulators that alter immune responses.
-
Subjects enrolled in France: the subject has participated in any study using an investigational drug during the previous 60 days or 5 half-lives, or twice the duration of the biological effect of the experimental drug or vaccine, whichever is longer, prior to screening for the study or the subject will participate simultaneously in another clinical study.
-
Any verified Grade 4 laboratory abnormality with the exception of Grade 4 lipid abnormalities (total cholesterol, triglycerides, high density lipoprotein [HDL] cholesterol, low density lipoprotein [LDL] cholesterol). A single repeat test is allowed during the Screening period to verify a result.
-
Any acute laboratory abnormality observed in ING117172 or in any Screening laboratory assessments for ING200336, which, in the opinion of the Investigator, would preclude the subject's participation in the study.
-
Hyperbilirubinemia of unknown etiology.
-
Confirmed (with no more than 1 repeat evaluation) Grade >= 2 urine protein (dipstick), serum creatinine, total bilirubin, alanine aminotransferase or aspartate aminotransferase at the time of the screening lab.
-
Subject has Creatinine Clearance of <50 mL/minute via Cockroft-Gault method at the time of the screening visit
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Orel | Russian Federation | 302040 | |
| 2 | GSK Investigational Site | St. Petersburg | Russian Federation | 196645 | |
| 3 | GSK Investigational Site | Madrid | Spain | 28046 |
Sponsors and Collaborators
- ViiV Healthcare
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, ViiV Healthcare
Study Documents (Full-Text)
More Information
Publications
None provided.- 200336
Study Results
Participant Flow
| Recruitment Details | The results presented are based on the primary analysis (and includes data up to a maximum of 292 weeks; data cut-off date: 15-Mar-2021). Additional results will be provided within one year after study completion. |
|---|---|
| Pre-assignment Detail | This is a single arm open-label study in women who became pregnant while participating in study ING117172 (NCT01910402). In this study 4 pregnant women were enrolled. Participant flow data was collected only in pregnant women (enrolled population/study participants) and not in infants, as infants were not considered as enrolled per study design. |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Period Title: Overall Study | |
| STARTED | 4 |
| Infants Born to Pregnant Women Who Received at Least One Dose of Study Treatment | 4 |
| COMPLETED | 1 |
| NOT COMPLETED | 3 |
Baseline Characteristics
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Overall Participants | 4 |
| Age (Years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [Years] |
29.3
(5.56)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
4
100%
|
| Male |
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | |
| White/Caucasian/European heritage |
4
100%
|
Outcome Measures
| Title | Area Under the Plasma Concentration Time Curve at Steady State During a Dosing Interval (AUC [0-tau]) for Dolutegravir |
|---|---|
| Description | Blood samples were collected at indicated timepoints for Pharmacokinetic (PK) analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum. |
| Time Frame | Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population consists of all participants in the Safety Population (comprised of all participants [pregnant women] who received at least one dose of study treatment) who had at least 1 non-missing PK assessment. |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Trimester 2 (Weeks 18-26 of pregnancy) |
55.045
|
| Trimester 3 (Weeks 30-36 of pregnancy) |
42.473
|
| 8-12 Weeks postpartum |
78.917
|
| Title | Maximum Observed Plasma Concentration (Cmax) for Dolutegravir |
|---|---|
| Description | Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum. |
| Time Frame | Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Trimester 2 (Weeks 18-26 of pregnancy) |
4.420
|
| Trimester 3 (Weeks 30-36 of pregnancy) |
3.424
|
| 8-12 Weeks Postpartum |
5.578
|
| Title | Drug Concentration at the End of Dosing Interval (Ctau) for Dolutegravir |
|---|---|
| Description | Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum. |
| Time Frame | 24 hours post dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Trimester 2 (Weeks 18-26 of pregnancy) |
930.1
|
| Trimester 3 (Weeks 30-36 of pregnancy) |
657.5
|
| 8-12 Weeks Postpartum |
2154.7
|
| Title | Apparent Oral Clearance (CL/F) for Dolutegravir |
|---|---|
| Description | Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum. |
| Time Frame | Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Trimester 2 (Weeks 18-26 of pregnancy) |
0.739
|
| Trimester 3 (Weeks 30-36 of pregnancy) |
0.952
|
| 8-12 Weeks Postpartum |
0.464
|
| Title | Steady State Volume of Distribution (Vss/F) After Extravascular Administration for Dolutegravir |
|---|---|
| Description | Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum. |
| Time Frame | Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Trimester 2 (Weeks 18-26 of pregnancy) |
9.665
|
| Trimester 3 (Weeks 30-36 of pregnancy) |
12.326
|
| 8-12 Weeks Postpartum |
6.326
|
| Title | Half-life (T1/2) for Dolutegravir |
|---|---|
| Description | Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum. |
| Time Frame | Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Trimester 2 (Weeks 18-26 of pregnancy) |
9.215
(1.8968)
|
| Trimester 3 (Weeks 30-36 of pregnancy) |
9.401
(3.0322)
|
| 8-12 Weeks Postpartum |
9.699
(3.0427)
|
| Title | Number of Participants (Pregnant Women) With Maximum Severity of Post-Baseline Emergent Hematology Toxicities: Hemoglobin |
|---|---|
| Description | Blood samples were collected for analysis of hemoglobin. Any abnormality was graded according to Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity scales from Grade 1 to 4 (1=Mild, 2=Moderate, 3=Severe, 4=Potentially life threatening). Number of participants (Pregnant Women) with maximum severity of post-Baseline emergent toxicities with respect to hemoglobin has been presented. |
| Time Frame | Up to Week 32 of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment. |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Grade 1 |
1
25%
|
| Grade 2 |
0
0%
|
| Grade 3 |
0
0%
|
| Grade 4 |
0
0%
|
| Title | Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) |
|---|---|
| Description | Blood samples were collected for the analysis of chemistry parameters including ALT and AST. |
| Time Frame | At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles). |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| ALT, Baseline (Day 1), n=4 |
10.8
(5.56)
|
| ALT, Week 4, n=4 |
15.3
(4.43)
|
| ALT, Week 8, n=4 |
19.3
(17.21)
|
| ALT, Week 12, n=4 |
11.0
(3.16)
|
| ALT, Week 16, n=4 |
10.8
(2.36)
|
| ALT, Week 20, n=4 |
10.3
(7.27)
|
| ALT, Week 24, n=1 |
19.0
(NA)
|
| ALT, Week 32, n=2 |
28.0
(15.56)
|
| AST, Baseline (Day 1), n=4 |
14.8
(4.19)
|
| AST, Week 4, n=4 |
17.3
(2.22)
|
| AST, Week 8, n=4 |
17.3
(6.18)
|
| AST, Week 12, n=4 |
15.0
(1.83)
|
| AST, Week 16, n=4 |
14.8
(2.63)
|
| AST, Week 20, n=4 |
16.3
(3.30)
|
| AST, Week 24, n=1 |
20.0
(NA)
|
| AST, Week 32, n=2 |
24.0
(8.49)
|
| Title | Change From Baseline in Chemistry Parameters: ALT and AST |
|---|---|
| Description | Blood samples were collected for the analysis of chemistry parameters including ALT and AST. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Time Frame | Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles). |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| ALT, Week 4, n=4 |
4.5
(6.03)
|
| ALT, Week 8, n=4 |
8.5
(11.79)
|
| ALT, Week 12, n=4 |
0.3
(3.30)
|
| ALT, Week 16, n=4 |
0.0
(3.56)
|
| ALT, Week 20, n=4 |
-0.5
(1.73)
|
| ALT, Week 24, n=1 |
0.0
(NA)
|
| ALT, Week 32, n=2 |
19.5
(14.85)
|
| AST, Week 4, n=4 |
2.5
(4.43)
|
| AST, Week 8, n=4 |
2.5
(2.38)
|
| AST, Week 12, n=4 |
0.3
(3.10)
|
| AST, Week 16, n=4 |
0.0
(3.37)
|
| AST, Week 20, n=4 |
1.5
(1.29)
|
| AST, Week 24, n=1 |
-1.0
(NA)
|
| AST, Week 32, n=2 |
11.0
(8.49)
|
| Title | Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine |
|---|---|
| Description | Blood samples were collected for the analysis of chemistry parameters including Bilirubin and Creatinine. |
| Time Frame | At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles). |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Bilirubin, Baseline (Day 1), n=4 |
7.3
(3.77)
|
| Bilirubin, Week 4, n=4 |
5.0
(1.83)
|
| Bilirubin, Week 8, n=4 |
5.5
(2.65)
|
| Bilirubin, Week 12, n=4 |
4.5
(1.29)
|
| Bilirubin, Week 16, n=4 |
4.5
(1.29)
|
| Bilirubin, Week 20, n=4 |
4.5
(1.29)
|
| Bilirubin, Week 24, n=1 |
7.0
(NA)
|
| Bilirubin, Week 32, n=2 |
6.5
(0.71)
|
| Creatinine, Baseline (Day 1), n=4 |
57.73
(16.661)
|
| Creatinine, Week 4, n=4 |
50.50
(2.990)
|
| Creatinine, Week 8, n=4 |
51.58
(3.067)
|
| Creatinine, Week 12, n=4 |
50.68
(3.293)
|
| Creatinine, Week 16, n=4 |
47.45
(2.001)
|
| Creatinine, Week 20, n=4 |
50.60
(6.424)
|
| Creatinine, Week 24, n=1 |
63.60
(NA)
|
| Creatinine, Week 32, n=2 |
68.90
(3.677)
|
| Title | Change From Baseline in Chemistry Parameters: Bilirubin and Creatinine |
|---|---|
| Description | Blood samples were collected for the analysis of chemistry parameters including Bilirubin and Creatinine. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Time Frame | Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles). |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Bilirubin, Week 4, n=4 |
-2.3
(2.06)
|
| Bilirubin, Week 8, n=4 |
-1.8
(1.26)
|
| Bilirubin, Week 12, n=4 |
-2.8
(2.99)
|
| Bilirubin, Week 16, n=4 |
-2.8
(2.99)
|
| Bilirubin, Week 20, n=4 |
-2.8
(2.99)
|
| Bilirubin, Week 24, n=1 |
-5.0
(NA)
|
| Bilirubin, Week 32, n=2 |
2.0
(2.83)
|
| Creatinine, Week 4, n=4 |
-7.23
(14.014)
|
| Creatinine, Week 8, n=4 |
-6.15
(16.700)
|
| Creatinine, Week 12, n=4 |
-7.05
(14.328)
|
| Creatinine, Week 16, n=4 |
-10.28
(17.453)
|
| Creatinine, Week 20, n=4 |
-7.13
(11.154)
|
| Creatinine, Week 24, n=1 |
-19.10
(NA)
|
| Creatinine, Week 32, n=2 |
19.10
(3.253)
|
| Title | Absolute Values of the Hematology Parameters: Hemoglobin |
|---|---|
| Description | Blood samples were collected for the analysis of hematology parameters including hemoglobin. |
| Time Frame | At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles). |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Baseline (Day 1), n=4 |
127.8
(11.24)
|
| Week 4, n=4 |
120.8
(7.23)
|
| Week 8, n=4 |
113.5
(7.05)
|
| Week 12, n=4 |
116.5
(7.14)
|
| Week 16, n=4 |
115.0
(4.69)
|
| Week 20, n=4 |
115.8
(8.30)
|
| Week 24, n=1 |
127.0
(NA)
|
| Week 32, n=2 |
140.5
(0.71)
|
| Title | Change From Baseline in Hematology Parameters: Hemoglobin |
|---|---|
| Description | Blood samples were collected for the analysis of hematology parameters including hemoglobin. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Time Frame | Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles). |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Week 4, n=4 |
-7.0
(10.17)
|
| Week 8, n=4 |
-14.3
(7.37)
|
| Week 12, n=4 |
-11.3
(4.92)
|
| Week 16, n=4 |
-12.8
(6.65)
|
| Week 20, n=4 |
-12.0
(4.97)
|
| Week 24, n=1 |
-14.0
(NA)
|
| Week 32, n=2 |
14.0
(8.49)
|
| Title | Absolute Values of the Hematology Parameters: Leukocytes and Platelets |
|---|---|
| Description | Blood samples were collected for the analysis of hematology parameters including leukocytes and platelets. |
| Time Frame | At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles). |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Leukocytes, Baseline (Day 1), n=4 |
6.48
(1.415)
|
| Leukocytes, Week 4, n=4 |
7.88
(2.095)
|
| Leukocytes, Week 8, n=4 |
8.43
(1.959)
|
| Leukocytes, Week 12, n=4 |
9.15
(2.053)
|
| Leukocytes, Week 16, n=4 |
9.23
(1.821)
|
| Leukocytes, Week 20, n=4 |
10.03
(2.848)
|
| Leukocytes, Week 24, n=1 |
12.60
(NA)
|
| Leukocytes, Week 32, n=2 |
5.85
(0.636)
|
| Platelets, Baseline (Day 1), n=4 |
204.8
(37.03)
|
| Platelets, Week 4, n=4 |
200.5
(2.38)
|
| Platelets, Week 8, n=4 |
220.8
(16.07)
|
| Platelets, Week 12, n=4 |
195.5
(25.38)
|
| Platelets, Week 16, n=4 |
198.0
(10.80)
|
| Platelets, Week 20, n=4 |
216.5
(10.91)
|
| Platelets, Week 24, n=1 |
250.0
(NA)
|
| Platelets, Week 32, n=2 |
206.0
(24.04)
|
| Title | Change From Baseline in Hematology Parameters: Leukocytes and Platelets |
|---|---|
| Description | Blood samples were collected for the analysis of hematology parameters including leukocytes and platelets. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Time Frame | Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24 and Week 32 of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles). |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Leukocytes, Week 4, n=4 |
1.40
(1.817)
|
| Leukocytes, Week 8, n=4 |
1.95
(2.047)
|
| Leukocytes, Week 12, n=4 |
2.68
(1.173)
|
| Leukocytes, Week 16, n=4 |
2.75
(1.654)
|
| Leukocytes, Week 20, n=4 |
3.55
(2.340)
|
| Leukocytes, Week 24, n=1 |
4.90
(NA)
|
| Leukocytes, Week 32, n=2 |
-0.65
(1.061)
|
| Platelets, Week 4, n=4 |
-4.3
(39.09)
|
| Platelets, Week 8, n=4 |
16.0
(33.44)
|
| Platelets, Week 12, n=4 |
-9.3
(39.08)
|
| Platelets, Week 16, n=4 |
-6.8
(47.16)
|
| Platelets, Week 20, n=4 |
11.8
(45.49)
|
| Platelets, Week 24, n=1 |
10.0
(NA)
|
| Platelets, Week 32, n=2 |
-4.0
(50.91)
|
| Title | Number of Participants (Pregnant Women) Who Discontinued the Treatment Due to Adverse Events (AE) |
|---|---|
| Description | An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a study treatment. Number of participants (pregnant women) who discontinued the treatment due to adverse events have been presented. |
| Time Frame | Up to Week 292 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Count of Participants [Participants] |
0
0%
|
| Title | Number of Participants (Pregnant Women) Demonstrated Congenital Malformations |
|---|---|
| Description | Data for participants (pregnant women) demonstrated congenital malformations was reported. |
| Time Frame | At delivery (up to Week 40 of pregnancy) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment. |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Count of Participants [Participants] |
0
0%
|
| Title | Time to Cmax (Tmax) for Dolutegravir |
|---|---|
| Description | Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum. |
| Time Frame | Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Trimester 2 (Weeks 18-26 of pregnancy) |
3.508
(1.7082)
|
| Trimester 3 (Weeks 30-36 of pregnancy) |
2.729
(0.4877)
|
| 8-12 Weeks Postpartum |
4.242
(2.0522)
|
| Title | Pre-dose Plasma Concentration (C0) for Dolutegravir |
|---|---|
| Description | Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum. |
| Time Frame | Pre-dose at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Pre-dose at Trimester 2 (Weeks 18-26 of pregnancy) |
666.9
|
| Trimester 3 (Weeks 30-36 of pregnancy) |
1084.6
|
| 8-12 Weeks Postpartum |
1225.0
|
| Title | Unbound DTG Concentrations in Plasma at 3 and 24 Hours Post Dose of Dolutegravir |
|---|---|
| Description | Blood samples were collected at indicated timepoints for PK analysis of dolutegravir at Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum. |
| Time Frame | At 3 hours and 24 hours post dose in Trimester 2 (Weeks 18-26 of pregnancy), Trimester 3 (Weeks 30-36 of pregnancy) and at 8-12 Weeks postpartum |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| At 3 hours post dose in Trimester 2 |
7.856
|
| At 3 hours post dose in Trimester 3 |
7.371
|
| At 3 hours post dose 8-12 Weeks postpartum |
6.898
|
| At 24 hours post dose in Trimester 2 |
1.798
|
| At 24 hours post dose in Trimester 3 |
2.065
|
| At 24 hours post dose 8-12 Weeks postpartum |
2.881
|
| Title | Total DTG Concentrations in Plasma From Cord Blood and Maternal Blood at the Time of Delivery |
|---|---|
| Description | Blood samples were collected at the time of delivery for PK analysis of dolutegravir. |
| Time Frame | At delivery (up to Week 40 of pregnancy) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Pharmacokinetic Population |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Cord plasma concentration |
1436.0
(1287.43)
|
| Maternal plasma concentration |
1806.3
(1125.04)
|
| Title | Number of Participants (Pregnant Women) With Treatment-emergent Genotypic and/or Phenotypic Resistance Who Met Confirmed Virologic Withdrawal Criteria |
|---|---|
| Description | Number of participants (pregnant women) with treatment-emergent genotypic and/or phenotypic resistance who met confirmed virologic withdrawal criteria are presented. Genotypic and phenotypic analyses were carried out by Monogram Biosciences using, but not limited to, their Standard Phenosense and GenoSure testing methods for protease (PRO) and reverse transcriptase (RT), or with their GeneSeq Integrase and PhenoSense Integrase assays. |
| Time Frame | Up to Week 32 of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Exposed (ITT-E) Population includes all participants (pregnant women) who received at least one dose of study treatment. |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Participants with genotypic resistance |
0
0%
|
| Participants with phenotypic resistance |
0
0%
|
| Title | Number of Participants (Pregnant Women) With Live Birth Outcome Categories |
|---|---|
| Description | Participants (pregnant women) with following live birth outcome categories are reported- Vaginal Birth, Planned Caesarean Section, Unscheduled Caesarean Section and Preterm Delivery. |
| Time Frame | At delivery (up to Week 40 of pregnancy) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment. |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Vaginal Birth |
1
25%
|
| Planned Caesarean Section |
2
50%
|
| Unscheduled Caesarean Section |
1
25%
|
| Preterm Delivery |
1
25%
|
| Title | Gestational Age of Infants |
|---|---|
| Description | Gestational age is defined as the number of weeks between the first day of the mother's last normal menstrual period and the day of birth. Data for gestational age of infants has been presented. |
| Time Frame | At birth |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on Infant Population which consisted of infants born to pregnant women who received at least one dose of study treatment. |
| Arm/Group Title | DTG/ABC/3TC - Infant |
|---|---|
| Arm/Group Description | This group consisted of Infants born to pregnant women who received a fixed dose combination tablet of dolutegravir, abacavir and lamivudine during pregnancy. |
| Measure Participants | 4 |
| Mean (Standard Deviation) [Weeks] |
38.3
(1.71)
|
| Title | Neonatal Length and Head Circumference at Birth |
|---|---|
| Description | Data for neonatal length and head circumference at birth are reported. |
| Time Frame | At birth |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on Infant Population which consisted of infants born to pregnant women who received at least one dose of study treatment. |
| Arm/Group Title | DTG/ABC/3TC - Infant |
|---|---|
| Arm/Group Description | This group consisted of Infants born to pregnant women who received a fixed dose combination tablet of dolutegravir, abacavir and lamivudine during pregnancy. |
| Measure Participants | 4 |
| Neonatal Length |
51.5
(3.11)
|
| Neonatal Head Circumference |
34.9
(1.65)
|
| Title | Neonatal Weight at Birth |
|---|---|
| Description | Data for neonatal weight at birth has been reported. |
| Time Frame | At birth |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on Infant Population which consisted of infants born to pregnant women who received at least one dose of study treatment. |
| Arm/Group Title | DTG/ABC/3TC - Infant |
|---|---|
| Arm/Group Description | This group consisted of Infants born to pregnant women who received a fixed dose combination tablet of dolutegravir, abacavir and lamivudine during pregnancy. |
| Measure Participants | 4 |
| Mean (Standard Deviation) [Grams] |
3262.5
(731.36)
|
| Title | Number of Infants by Their Weight Categories at Birth |
|---|---|
| Description | Weight of infants at birth were categorized as: Small for Gestational Age (SGA) defined neonates under the 10th percentile in weight, Appropriate for Gestational Age (AGA) characterized neonates between the 10th and 90th percentiles in weight and Large for Gestational Age (LGA) referred to neonates over the 90th percentile in weight. |
| Time Frame | At birth |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on Infant Population which consisted of infants born to pregnant women who received at least one dose of study treatment. |
| Arm/Group Title | DTG/ABC/3TC - Infant |
|---|---|
| Arm/Group Description | This group consisted of Infants born to pregnant women who received a fixed dose combination tablet of dolutegravir, abacavir and lamivudine during pregnancy. |
| Measure Participants | 4 |
| LGA |
0
0%
|
| AGA |
4
100%
|
| SGA |
0
0%
|
| Title | Number of Infants by Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) Score at 1 and 5 Minutes After Birth |
|---|---|
| Description | APGAR is a quick test to assess the health of new born. The test is performed at 1 and 5 minutes after birth. APGAR scale is determined by evaluating the new born on five categories (appearance, pulse, grimace, activity and respiration) on a scale from zero to two with 2 being the best score, then summing up the values obtained from all five categories. APGAR score ranges from 0 to 10 (Higher score indicates better health) where a score of 7 and above is normal. Number of infants by APGAR score at 1 and 5 minutes after birth are presented. |
| Time Frame | 1 and 5 minutes after birth |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on Infant Population which consisted of infants born to pregnant women who received at least one dose of study treatment. |
| Arm/Group Title | DTG/ABC/3TC - Infant |
|---|---|
| Arm/Group Description | This group consisted of Infants born to pregnant women who received a fixed dose combination tablet of dolutegravir, abacavir and lamivudine during pregnancy. |
| Measure Participants | 4 |
| 1 Minute, Score 0 to 6 |
0
0%
|
| 1 Minute, Score 7 to 10 |
4
100%
|
| 5 Minute, Score 0 to 6 |
0
0%
|
| 5 Minute, Score 7 to 10 |
4
100%
|
| Title | Percentage of Participants (Pregnant Women) With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) by Visit |
|---|---|
| Description | Percentage of participants (pregnant women) with plasma HIV-1 RNA <50 c/mL are presented. Plasma samples were collected for quantitative analysis of HIV-1 RNA. |
| Time Frame | At Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 and Week 32 of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Exposed Population. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles). |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Week 4, n=4 |
100
2500%
|
| Week 8, n=4 |
100
2500%
|
| Week 12, n=4 |
100
2500%
|
| Week 16, n=4 |
100
2500%
|
| Week 20, n=4 |
100
2500%
|
| Week 24, n=2 |
100
2500%
|
| Week 28, n=1 |
100
2500%
|
| Week 32, n=2 |
100
2500%
|
| Title | Percentage of Participants (Pregnant Women) With Plasma HIV-1 RNA <400 c/mL by Visit |
|---|---|
| Description | Percentage of participants (pregnant women) with plasma HIV-1 RNA <400 c/mL are presented. Plasma samples were collected for quantitative analysis of HIV-1 RNA. |
| Time Frame | At Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 and Week 32 of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Exposed Population. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles) |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Week 4, n=4 |
100
2500%
|
| Week 8, n=4 |
100
2500%
|
| Week 12, n=4 |
100
2500%
|
| Week 16, n=4 |
100
2500%
|
| Week 20, n=4 |
100
2500%
|
| Week 24, n=2 |
100
2500%
|
| Week 28, n=1 |
100
2500%
|
| Week 32, n=2 |
100
2500%
|
| Title | Absolute Values of Cluster of Differentiation 4 (CD4+) T Cell Counts by Visit |
|---|---|
| Description | Blood samples were collected for the analysis of CD4+ T cell counts using cytometry. |
| Time Frame | At Baseline (Day 1), Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 and Week 32 of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Exposed Population. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles). |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Baseline (Day 1), n=4 |
476.3
(123.31)
|
| Week 4, n=4 |
569.5
(238.51)
|
| Week 8, n=4 |
569.8
(296.43)
|
| Week 12, n=4 |
575.0
(331.22)
|
| Week 16, n=4 |
626.8
(270.63)
|
| Week 20, n=4 |
791.5
(524.96)
|
| Week 24, n=2 |
874.5
(516.90)
|
| Week 28, n=1 |
488.0
(NA)
|
| Week 32, n=2 |
677.5
(40.31)
|
| Title | Change From Baseline in CD4+ T Cell Counts by Visit |
|---|---|
| Description | Blood samples were collected for the analysis of CD4+ T cell counts using cytometry. Baseline value (Day 1) is the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline is defined as post-dose visit value minus Baseline value. |
| Time Frame | Baseline and at Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28 and Week 32 of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Exposed Population. Only those participants (pregnant women) with data available at the specified data points were analyzed (represented by n=X in the category titles). |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Week 4, n=4 |
93.3
(124.64)
|
| Week 8, n=4 |
93.5
(174.54)
|
| Week 12, n=4 |
98.8
(208.50)
|
| Week 16, n=4 |
150.5
(148.73)
|
| Week 20, n=4 |
315.3
(402.00)
|
| Week 24, n=2 |
353.0
(332.34)
|
| Week 28, n=1 |
98.0
(NA)
|
| Week 32, n=2 |
246.0
(97.58)
|
| Title | Number of Participants (Pregnant Women) With Disease Progression |
|---|---|
| Description | Disease progression included HIV-associated conditions, acquired immunodeficiency syndrome (AIDS) and death. Number of participants (pregnant women) with disease progression to Centers for Disease Control and Prevention (CDC) class C or death have been presented. |
| Time Frame | Up to Week 32 of study |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-Treat Exposed Population |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Count of Participants [Participants] |
0
0%
|
| Title | Number of Participants (Pregnant Women) With Adverse Events (AE) as Per Severity Grades |
|---|---|
| Description | Number of participants (pregnant women) with adverse events (AE) as per severity grades were presented. Grade 1 is mild, grade 2 is moderate, grade 3 is severe or medically significant but not immediately life-threatening and grade 4 is life-threatening consequences; urgent intervention required. |
| Time Frame | Up to 292 Weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety Population comprised of all participants (Pregnant Women) who received at least one dose of study treatment |
| Arm/Group Title | DTG/ABC/3TC - Mother |
|---|---|
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. |
| Measure Participants | 4 |
| Grade 1 |
2
50%
|
| Grade 2 |
2
50%
|
| Grade 3 |
0
0%
|
| Grade 4 |
0
0%
|
Adverse Events
| Time Frame | All-cause mortality, serious adverse events and non-serious adverse events were collected up to a maximum of 292 weeks (data cut-off date: 15-Mar-2021) | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Safety population comprised of all pregnant women who received at least one dose of study treatment. All-Cause Mortality and Adverse events data was collected only in pregnant women (enrolled population/study participants) and not in infants, as infants were not considered as enrolled per study design. The results presented are based on the Primary analysis up to a maximum of 292weeks (data cut-off date:15-Mar-2021), and additional results will be provided within one year after study completion. | |||
| Arm/Group Title | DTG/ABC/3TC - Mother | DTG/ABC/3TC - Infant | ||
| Arm/Group Description | Participants (pregnant women) received fixed dose combination (FDC) tablet of dolutegravir (DTG) 50 milligrams (mg), abacavir (ABC) 600 mg and lamivudine (3TC) 300 mg once daily, with or without food. | This group consisted of Infants born to pregnant women who received a fixed dose combination tablet of dolutegravir, abacavir and lamivudine during pregnancy. | ||
All Cause Mortality |
||||
| DTG/ABC/3TC - Mother | DTG/ABC/3TC - Infant | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/4 (0%) | 0/0 (NaN) | ||
Serious Adverse Events |
||||
| DTG/ABC/3TC - Mother | DTG/ABC/3TC - Infant | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/4 (25%) | 0/0 (NaN) | ||
| Pregnancy, puerperium and perinatal conditions | ||||
| Premature baby | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| DTG/ABC/3TC - Mother | DTG/ABC/3TC - Infant | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | 0/0 (NaN) | ||
| Gastrointestinal disorders | ||||
| Dyspepsia | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
| General disorders | ||||
| Asthenia | 2/4 (50%) | 2 | 0/0 (NaN) | 0 |
| Infections and infestations | ||||
| Respiratory tract infection | 2/4 (50%) | 5 | 0/0 (NaN) | 0 |
| Cystitis | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
| Gastroenteritis | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
| Oral herpes | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
| Respiratory tract infection viral | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
| Vaginal infection | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
| Musculoskeletal and connective tissue disorders | ||||
| Intervertebral disc protrusion | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
| Nervous system disorders | ||||
| Headache | 2/4 (50%) | 2 | 0/0 (NaN) | 0 |
| Migraine | 1/4 (25%) | 2 | 0/0 (NaN) | 0 |
| Renal and urinary disorders | ||||
| Nephropathy | 2/4 (50%) | 4 | 0/0 (NaN) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Alopecia | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
| Dermatitis allergic | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
| Vascular disorders | ||||
| Hypertension | 1/4 (25%) | 1 | 0/0 (NaN) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
| Name/Title | GSK Response Center |
|---|---|
| Organization | ViiV Healthcare |
| Phone | 866-435-7343 |
| GSKClinicalSupportHD@gsk.com |
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