ING200336, Pharmacokinetic and Safety Study in Pregnant Women With Human Immuno Virus Infection

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2014 by GlaxoSmithKline
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02075593
First received: February 27, 2014
Last updated: September 29, 2014
Last verified: July 2014
  Purpose

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 Intervention Phase
Infection, Human Immunodeficiency Virus
Drug: DTG 50 mg /ABC 600 mg /3TC 300 mg FDC tablets
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: ING200336: A Prospective, Interventional Pharmacokinetic and Safety Study of DTG/ABC/3TC in Pregnant Women

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Describe the DTG PK parameters during the third trimester of pregnancy (Weeks 18-26 and Weeks 30-36) and at 8-12 weeks postpartum [ Time Frame: PK samples will be collected at pre-dose, and at 1, 2, 3, 4, 6, 8, 12, and 24 hours post dose at each PK visit ] [ Designated as safety issue: No ]
    PK parameters include: area under the concentration time curve during the dosing interval (AUC [0-tau]), maximum drug concentration (Cmax), drug concentration at the end of dosing interval (Ctau), apparent clearance (CL/F), steady state volume of distribution (Vss/F), and half life (t1/2). PK samples will be collected at weeks 30-36 of pregnancy and 8-12 weeks post pregnancy.

  • Incidence and severity of adverse events (AEs). [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    All AEs and serious AEs will be collected from Day 1 through to the Continuation phase regardless of relationship to study participation or any other causality.

  • Incidence and severity of laboratory abnormalities [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Laboratory parameters include: hematology, clinical chemistry and urinalysis

  • Absolute values and change over time in laboratory parameters [ Time Frame: Baseline and up to 3 years ] [ Designated as safety issue: No ]
    Laboratory parameters include: hematology, clinical chemistry and urinalysis. Change will be measured as Baseline value minus values at the indicated time points

  • Number of subjects who discontinue study due to AE [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Number of pregnancies with and without demonstrated congenital [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    To characterize the safety of DTG/ABC/3TC FDC to the developing fetus.


Secondary Outcome Measures:
  • PK profile (Tmax and C0) during the third trimester of pregnancy (Weeks 18-26 and Weeks 30-36) and at 8-12 weeks postpartum [ Time Frame: PK samples will be collected at pre-dose, and at 1, 2, 3, 4, 6, 8, 12, and 24 hours post dose at each PK visit. ] [ Designated as safety issue: No ]
    PK parameters include: drug concentration immediately prior to dosing at steady state (C0) and time to Cmax (Tmax).

  • DTG PK parameters during the second trimester of pregnancy (Weeks 18-26). [ Time Frame: PK samples will be collected at pre-dose, and at 1, 2, 3, 4, 6, 8, 12, and 24 hours post dose at each PK visit. ] [ Designated as safety issue: No ]
    PK parameters include: AUC (0-tau), Cmax, Ctau, C0, Tmax, CL/F, Vss/F and t1/2

  • Unbound DTG concentrations in plasma during the second and third trimesters (Weeks 18-26 and Weeks 30-36) and at 8-12 weeks postpartum [ Time Frame: PK samples will be collected at 3 and 24 hours post dose at the PK visits. ] [ Designated as safety issue: No ]
    Blood samples will be collected during study visits within Weeks 18-26 and Weeks 30-36 of pregnancy, and at 8-12 Weeks post partum

  • Total DTG concentrations in plasma from cord blood compared to those in maternal [ Time Frame: At delivery and if possible, within 30 minutes of each other ] [ Designated as safety issue: No ]
    If feasible, a cord and maternal blood sample will also be collected at delivery.

  • Incidence of treatment-emergent genotypic and/or phenotypic resistance in subjects who meet confirmed virologic withdrawal criteria [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
  • Characterization of pregnancy outcomes [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Pregnancy outcomes include: Caesarean section, premature rupture of membranes, pre-term labor [prior to Week 37 of pregnancy], pre-term delivery, preeclampsia, eclampsia, hemolysis elevated-liver enzymes-low platelet count, pre-gestational diabetes, gestational diabetes, hypertension, multiple gestation, chromosomal abnormalities, intrauterine infection, and drug-induced hepatitis).

  • Characterization of infant outcomes [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Infant outcomes include: infant gestational age, length, weight (including percentiles, small gestational age, adequate gestational age, large gestational age, intrauterine growth restriction), and head circumference, and presence or absence of major congenital abnormalities at birth.

  • Number of subjects with plasma HIV-1 Ribonucleic Acid (RNA) < 50 copies/milliliter (c/mL) over time [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    A plasma HIV-1 RNA sample will be drawn at each visit, within 24 hours of delivery and on the day of the post-partum PK evaluation

  • Number of subjects with plasma HIV-1 RNA < 400 c/mL over time [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    A plasma HIV-1 RNA sample will be drawn at each visit, within 24 hours of delivery and on the day of the post-partum PK evaluation

  • Absolute values and changes from Baseline in cluster of differentiation 4 (CD4+) T cell counts over time [ Time Frame: Baseline and up to 3 years ] [ Designated as safety issue: No ]
    A CD4+ cell count sample will be drawn at each visit, within 24 hours of delivery and on the day of the post-partum PK evaluation

  • Incidence of disease progression (HIV-associated conditions, acquired immunodeficiency syndrome [AIDS] and death). [ Time Frame: Up to 3 years ] [ Designated as safety issue: No ]
    Assessed at each study visit


Estimated Enrollment: 25
Study Start Date: October 2014
Estimated Study Completion Date: February 2019
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02075593

Contacts
Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com

Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02075593     History of Changes
Other Study ID Numbers: 200336
Study First Received: February 27, 2014
Last Updated: September 29, 2014
Health Authority: Mexico: Ministry of Health
Russia: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Thailand: Food and Drug Administration, Thailand
South Africa: Medicines Control Council
Portugal: National Authority of Medicines and Health Products
Argentina: Ministry of Health
Italy: Italian Medicines Agency
Spain: Spanish Agency for Medicines and Health Products
France: National Agency for the Safety of Medicine and Health Products
Canada: Health Canada

Keywords provided by GlaxoSmithKline:
dolutegravir/abacavir/lamivudine fixed dose combination
pregnant women
once daily
antiretroviral therapy-naive
HIV-1 Infection
integrase inhibitor

Additional relevant MeSH terms:
Infection
Communicable Diseases
Immunologic Deficiency Syndromes
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases

ClinicalTrials.gov processed this record on October 19, 2014