Phase 3
N=4
ING200336, Pharmacokinetic and Safety Study in Pregnant Women With Human Immuno Virus Infection
Infection, Human Immunodeficiency Virus · HIV Infections · Arthralgia
Bottom Line
View on ClinicalTrials.gov: NCT02075593 ↗Enrolled (actual)
4
Serious AEs
25.0%
Results posted
Feb 2022
Primary outcome: Primary: Area Under the Plasma Concentration Time Curve at Steady State During a Dosing Interval (AUC [0-tau]) for Dolutegravir — 55.045; 42.473; 78.917 Micrograms*hours per milliliter
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- DTG 50 mg /ABC 600 mg /3TC 300 mg FDC tablets (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- Female
- Sponsor
- ViiV Healthcare
- Primary completion
- Oct 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Plasma Concentration Time Curve at Steady State During a Dosing Interval (AUC [0-tau]) for Dolutegravir |
55.045; 42.473; 78.917 | — |
| PRIMARY Maximum Observed Plasma Concentration (Cmax) for Dolutegravir |
4.420; 3.424; 5.578 | — |
| PRIMARY Drug Concentration at the End of Dosing Interval (Ctau) for Dolutegravir |
930.1; 657.5; 2154.7 | — |
| PRIMARY Apparent Oral Clearance (CL/F) for Dolutegravir |
0.739; 0.952; 0.464 | — |
| PRIMARY Steady State Volume of Distribution (Vss/F) After Extravascular Administration for Dolutegravir |
9.665; 12.326; 6.326 | — |
| PRIMARY Half-life (T1/2) for Dolutegravir |
9.215; 9.401; 9.699 | — |
| PRIMARY Number of Participants (Pregnant Women) With Maximum Severity of Post-Baseline Emergent Hematology Toxicities: Hemoglobin |
1; 0; 0; 0 | — |
| PRIMARY Absolute Values of the Chemistry Parameters: Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) |
10.8; 15.3; 19.3; 11.0; 10.8; 10.3 | — |
| PRIMARY Change From Baseline in Chemistry Parameters: ALT and AST |
4.5; 8.5; 0.3; 0.0; -0.5; 0.0 | — |
| PRIMARY Absolute Values of the Chemistry Parameters: Bilirubin and Creatinine |
7.3; 5.0; 5.5; 4.5; 4.5; 4.5 | — |
| PRIMARY Change From Baseline in Chemistry Parameters: Bilirubin and Creatinine |
-2.3; -1.8; -2.8; -2.8; -2.8; -5.0 | — |
| PRIMARY Absolute Values of the Hematology Parameters: Hemoglobin |
127.8; 120.8; 113.5; 116.5; 115.0; 115.8 | — |
| PRIMARY Change From Baseline in Hematology Parameters: Hemoglobin |
-7.0; -14.3; -11.3; -12.8; -12.0; -14.0 | — |
| PRIMARY Absolute Values of the Hematology Parameters: Leukocytes and Platelets |
6.48; 7.88; 8.43; 9.15; 9.23; 10.03 | — |
| PRIMARY Change From Baseline in Hematology Parameters: Leukocytes and Platelets |
1.40; 1.95; 2.68; 2.75; 3.55; 4.90 | — |
| PRIMARY Number of Participants (Pregnant Women) Who Discontinued the Treatment Due to Adverse Events (AE) |
— | — |
| PRIMARY Number of Participants (Pregnant Women) Demonstrated Congenital Malformations |
— | — |
| PRIMARY Number of Participants (Pregnant Women) With Adverse Events (AE) as Per Severity Grades |
2; 2; 0; 0 | — |
| SECONDARY Time to Cmax (Tmax) for Dolutegravir |
3.508; 2.729; 4.242 | — |
| SECONDARY Pre-dose Plasma Concentration (C0) for Dolutegravir |
666.9; 1084.6; 1225.0 | — |
| SECONDARY Unbound DTG Concentrations in Plasma at 3 and 24 Hours Post Dose of Dolutegravir |
7.856; 7.371; 6.898; 1.798; 2.065; 2.881 | — |
| SECONDARY Total DTG Concentrations in Plasma From Cord Blood and Maternal Blood at the Time of Delivery |
1436.0; 1806.3 | — |
| SECONDARY Number of Participants (Pregnant Women) With Treatment-emergent Genotypic and/or Phenotypic Resistance Who Met Confirmed Virologic Withdrawal Criteria |
0; 0 | — |
| SECONDARY Number of Participants (Pregnant Women) With Live Birth Outcome Categories |
1; 2; 1; 1 | — |
| SECONDARY Gestational Age of Infants |
38.3 | — |
| SECONDARY Neonatal Length and Head Circumference at Birth |
51.5; 34.9 | — |
| SECONDARY Neonatal Weight at Birth |
3262.5 | — |
| SECONDARY Number of Infants by Their Weight Categories at Birth |
0; 4; 0 | — |
| SECONDARY Number of Infants by Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) Score at 1 and 5 Minutes After Birth |
0; 4; 0; 4 | — |
| SECONDARY Percentage of Participants (Pregnant Women) With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) by Visit |
100; 100; 100; 100; 100; 100 | — |
| SECONDARY Percentage of Participants (Pregnant Women) With Plasma HIV-1 RNA <400 c/mL by Visit |
100; 100; 100; 100; 100; 100 | — |
| SECONDARY Absolute Values of Cluster of Differentiation 4 (CD4+) T Cell Counts by Visit |
476.3; 569.5; 569.8; 575.0; 626.8; 791.5 | — |
| SECONDARY Change From Baseline in CD4+ T Cell Counts by Visit |
93.3; 93.5; 98.8; 150.5; 315.3; 353.0 | — |
| SECONDARY Number of Participants (Pregnant Women) With Disease Progression |
— | — |
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.
Eligibility 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 = 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
Data sourced from ClinicalTrials.gov (NCT02075593). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.