Back to resultsSingle Dose Pharmacokinetics of Doravirine in HIV-infected Pregnant Women
Primary Purpose
HIV Infections, Pregnancy Related
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Doravirine
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infections
Eligibility Criteria
Inclusion Criteria:
- Pregnant women living with Human Immunodeficiency Virus (HIV) ≥18 years of age
- Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
- Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the trial.
- On stable combination Antiretroviral Therapy (cART) for at least 30 days prior to enrollment
- Plasma HIV RNA < 50 copies/mL within 90 days prior to enrollment
Ability and willingness of participant to not change their cART regimen to avoid any confounding of pharmacokinetic (PK) parameters.
o Note: Women who change cART regimens will be replaced.
- Aspartate aminotransferase and alanine aminotransferase < 3x Upper Limit of Normal (ULN)
- Hemoglobin lower than Division of AIDs (Acquired Immunodeficiency Syndrome) (DAIDs) Grade 2 (9.0 g/dL)
Exclusion Criteria:
- Women with multiple gestation, active opportunistic infections, present obstetrical complications that would deem them unsuitable for study participation, or evidence of fetal anomalies in present pregnancy will be excluded.
- Women with severe renal impairment, end stage renal disease, undergoing dialysis, or severe hepatic impairment (Child-Pugh C)
- Women with a significant illness/condition at the time of enrollment that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence or assessment of safety.
- Women with pregnancies that have become complicated are excluded for safety reasons.
- Active hepatitis C (HCV) infection as defined by anti-hepatitis C virus serology (as determined by multi-antigen EIA) and detectable HCV RNA.
- Clinically significant labs greater than Grade 2 on the NIH Division of AIDs Table for Grading the Severity of Adult and Pediatric Adverse events
- Receiving CYP3A inducers including carbamazepine, phenobarbital, phenytoin, enzalutamide, rifampin, rifapentine, mitotane, or St. John's wort or other drugs, including antiretrovirals, that influence drug concentration or alter pharmacokinetic profiles (atazanavir, maraviroc, darunavir, norvir, efavirenz, tipranavir)
- Receiving moderate to strong cytochrome p450 3A (CYP3A) inhibitors including clarithromycin, boceprevir, cobicistat, danoprevir and ritonavir, elvitegravir and ritonavir, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, paritaprevir and ritonavir, posaconazole, ritonavir, saquinavir and ritonavir, telaprevir, tipranavir and ritonavir, grapefruit juice, idelalisib, nefazodone, and nelfinavir.
Sites / Locations
- University of North Carolina at Chapel HillRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Doravirine
Arm Description
100mg doravirine given by mouth once at each sampling visit.
Outcomes
Primary Outcome Measures
Change in total and protein-unbound Cmax of doravirine in blood plasma during pregnancy.
To describe single-dose total and protein-unbound Cmax of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum
Change in total and protein-unbound Tmax of doravirine in blood plasma during pregnancy.
To describe single-dose total and protein-unbound Tmax of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum
Change in total and protein-unbound C12h of doravirine in blood plasma during pregnancy.
To describe single-dose total and protein-unbound C12h of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum
Change in total and protein-unbound C24h of doravirine in blood plasma during pregnancy.
To describe single-dose total and protein-unbound C24h of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum
Change in total and protein-unbound Area Under the Curve (AUC) of doravirine in blood plasma during pregnancy.
To describe single-dose total and protein-unbound AUC of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum
Secondary Outcome Measures
Number of Adverse Events reported after single doses of doravirine in pregnant participants.
To evaluate the number of Adverse Events reported after single doses of doravirine in pregnant participants living with HIV
Full Information
NCT ID
NCT04900974
First Posted
May 13, 2021
Last Updated
April 12, 2023
Sponsor
University of North Carolina, Chapel Hill
Collaborators
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT04900974
Brief Title
Single Dose Pharmacokinetics of Doravirine in HIV-infected Pregnant Women
Official Title
Single Dose Pharmacokinetics of Doravirine in HIV-infected Pregnant Women
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 9, 2022 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
March 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this research study is to evaluate the effect of body changes in pregnancy on doravirine concentrations, to determine what dose of doravirine should be used. Study participants will remain on their normal antiretroviral medications (ARVs) while participating in this study as prescribed by their regular clinic provider. Study participants will come to the research clinic for three sampling visits throughout their time as a participant. Study participants will only take one dose of doravirine during each sampling visit, which will occur during the 2nd and 3rd trimesters, as well as after their baby is delivered. This study was designed intentionally to not give a dose of doravirine in the first trimester when there is the greatest chance for all drugs to potentially cause injury to the baby. Study participants that choose to participate in this study may be enrolled for up to 10 months depending on the length of their pregnancy and how the visits are scheduled.
Detailed Description
Antiretroviral (ARV) medications are used to treat infection with human immunodeficiency virus (HIV). During pregnancy, ARV therapy keeps women healthy and decreases the spread of HIV to their babies (<1-2%).
Many changes occur in the body during pregnancy, which can alter the concentrations of drug in the body. Doravirine (DOR) is a Food and Drug Administration (FDA) approved ARV, but the extent to which the drug concentrations of doravirine change during pregnancy is unknown. Because these changes are unknown, DOR has not been approved by the FDA for use among pregnant women; however, the FDA has given the researchers permission to use it in this study Pregnant women are often excluded from clinical trials, so it can take several years after a drug gets approved before contemporary ARV is available to them.
The purpose of this research study is to evaluate the effect of body changes in pregnancy on doravirine concentrations, to determine what dose of doravirine should be used. Study participants will remain on their normal antiretroviral medications (ARVs) while participating in this study as prescribed by their regular clinic provider. Study participants will come to the research clinic for three sampling visits throughout their time as a participant. Study participants will only take one dose of doravirine during each sampling visit, which will occur during the 2nd and 3rd trimesters, as well as after their baby is delivered. This study was designed intentionally to not give a dose of doravirine in the first trimester when there is the greatest chance for all drugs to potentially cause injury to the baby. Study participants that choose to participate in this study may be enrolled for up to 10 months depending on the length of their pregnancy and how the visits are scheduled.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Pregnancy Related
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Doravirine
Arm Type
Experimental
Arm Description
100mg doravirine given by mouth once at each sampling visit.
Intervention Type
Drug
Intervention Name(s)
Doravirine
Intervention Description
100mg
Primary Outcome Measure Information:
Title
Change in total and protein-unbound Cmax of doravirine in blood plasma during pregnancy.
Description
To describe single-dose total and protein-unbound Cmax of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum
Time Frame
Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 and hours post-dose in each period.
Title
Change in total and protein-unbound Tmax of doravirine in blood plasma during pregnancy.
Description
To describe single-dose total and protein-unbound Tmax of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum
Time Frame
Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 and hours post-dose in each period.
Title
Change in total and protein-unbound C12h of doravirine in blood plasma during pregnancy.
Description
To describe single-dose total and protein-unbound C12h of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum
Time Frame
Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 and hours post-dose in each period.
Title
Change in total and protein-unbound C24h of doravirine in blood plasma during pregnancy.
Description
To describe single-dose total and protein-unbound C24h of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum
Time Frame
Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 and hours post-dose in each period.
Title
Change in total and protein-unbound Area Under the Curve (AUC) of doravirine in blood plasma during pregnancy.
Description
To describe single-dose total and protein-unbound AUC of doravirine in the blood plasma of women living with HIV during the 2nd trimester, 3rd trimester, and post-partum
Time Frame
Pre-dose (within 1 hour prior to dosing) and at 0.5, 1, 2, 4, 6, 8, 10, 12, 24, 48, 72 and hours post-dose in each period.
Secondary Outcome Measure Information:
Title
Number of Adverse Events reported after single doses of doravirine in pregnant participants.
Description
To evaluate the number of Adverse Events reported after single doses of doravirine in pregnant participants living with HIV
Time Frame
From enrollment visit to follow-up visit, an average of 10 months.
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Pregnant women living with Human Immunodeficiency Virus (HIV) ≥18 years of age
Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other trial procedures.
Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the trial.
On stable combination Antiretroviral Therapy (cART) for at least 30 days prior to enrollment
Plasma HIV RNA < 50 copies/mL within 90 days prior to enrollment
Ability and willingness of participant to not change their cART regimen to avoid any confounding of pharmacokinetic (PK) parameters.
o Note: Women who change cART regimens will be replaced.
Aspartate aminotransferase and alanine aminotransferase < 3x Upper Limit of Normal (ULN)
Hemoglobin lower than Division of AIDs (Acquired Immunodeficiency Syndrome) (DAIDs) Grade 2 (9.0 g/dL)
Exclusion Criteria:
Women with multiple gestation, active opportunistic infections, present obstetrical complications that would deem them unsuitable for study participation, or evidence of fetal anomalies in present pregnancy will be excluded.
Women with severe renal impairment, end stage renal disease, undergoing dialysis, or severe hepatic impairment (Child-Pugh C)
Women with a significant illness/condition at the time of enrollment that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence or assessment of safety.
Women with pregnancies that have become complicated are excluded for safety reasons.
Active hepatitis C (HCV) infection as defined by anti-hepatitis C virus serology (as determined by multi-antigen EIA) and detectable HCV RNA.
Clinically significant labs greater than Grade 2 on the NIH Division of AIDs Table for Grading the Severity of Adult and Pediatric Adverse events
Receiving CYP3A inducers including carbamazepine, phenobarbital, phenytoin, enzalutamide, rifampin, rifapentine, mitotane, or St. John's wort or other drugs, including antiretrovirals, that influence drug concentration or alter pharmacokinetic profiles (atazanavir, maraviroc, darunavir, norvir, efavirenz, tipranavir)
Receiving moderate to strong cytochrome p450 3A (CYP3A) inhibitors including clarithromycin, boceprevir, cobicistat, danoprevir and ritonavir, elvitegravir and ritonavir, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, paritaprevir and ritonavir, posaconazole, ritonavir, saquinavir and ritonavir, telaprevir, tipranavir and ritonavir, grapefruit juice, idelalisib, nefazodone, and nelfinavir.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Amanda Poliseno, BS
Phone
919-962-5344
Email
amanda_poliseno@unc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Angela Kashuba, PharmD
Organizational Affiliation
UNC Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Amanda Poliseno
Phone
919-962-5344
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
IPD Sharing Time Frame
Beginning 9 to 36 months following publication.
Learn more about this trial
Single Dose Pharmacokinetics of Doravirine in HIV-infected Pregnant Women
We'll reach out to this number within 24 hrs