HIV InfectionsPhase 1NCT02778204
Evaluating the Safety and Pharmacokinetics of Maraviroc in HIV-1-Exposed Infants at Risk of Acquiring HIV-1 Infection
A Phase 1 study testing Maraviroc in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 9 sites in 4 countries.
Trial summary
This study aimed to evaluate the safety, tolerability, and pharmacokinetics of maraviroc in infants at risk for mother-to-child HIV transmission, and to determine an appropriate dose of maraviroc during the first six weeks of life. Read more about this study
- Who is it for?
- Ages Up to 3 days
- Conditions the study is for
- HIV Infections
- What is being tested?
- Maraviroc
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 9 sitesin 4 countries
- Study dates
- 5 Jun 2017to 20 Nov 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 3 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Mother was of legal age to provide independent informed consent for research participation and was willing and able to provide written informed consent for her and her infant's participation in this study.
- Mother had confirmed HIV-1 infection based on testing of two samples collected at different time points. More information on this criterion can be found in the protocol.
- At entry, infant met EFV exposure requirements, based on mother's report and confirmed by medical records if available, as follows:
- For Cohort 1, Stratum 1A: Infant born to a mother who did not receive EFV during the eight weeks immediately prior to delivery. Note: Breastfeeding and formula feeding infants were eligible for this stratum.
- For Cohort 1, Stratum 1B: Infant born to a mother who received EFV for a minimum of two weeks immediately prior to delivery. Note: Breastfeeding and formula feeding infants were eligible for this stratum.
- For Cohort 2, Stratum 2A: Infants born to a mother who did not receive EFV during the eight weeks immediately prior to delivery and if breastfeeding, mother was not receiving maternal EFV. Note: Breastfeeding and formula feeding infants were eligible for this stratum.
Show all 17Show fewer
- For Cohort 2, Stratum 2B: Breastfeeding infants born to a mother who received EFV for a minimum of two weeks immediately prior to delivery, intended to breastfeed for a minimum of six weeks and continued to receive maternal EFV while breastfeeding. Note: Only breastfeeding infants were eligible for this stratum.
- At birth, infant's estimated gestational age was at least 37 weeks. Note: If gestational age at birth is not documented in the infant's available birth records, study staff may assess gestational age at the earliest possible opportunity during the screening period and use this assessment for purposes of eligibility determination.
- At birth, infant's weight was at least 2 kg. Note: If weight at birth is not documented in the infant's available birth records, study staff may assess infant weight at the earliest possible opportunity during the screening period and use this assessment for purposes of eligibility determination.
- At entry, infant was less than or equal to 3 days old.
- At entry, infant had the following lab values:
- Grade 0 alanine transaminase (ALT) (normal)
- Less than or equal to Grade 1 aspartate aminotransferase (AST) and total bilirubin
- Less than or equal to Grade 2 hemoglobin, white blood cell counts, platelet counts
- At entry, infant had initiated antiretroviral prophylaxis that did not include a potent CYP3A4 inhibitor or inducer. See the protocol for more information.
- At entry, infant was assessed by the site investigator or designee as generally healthy based on review of available medical records, other available medical history information, and physical examination findings.
- Born after singleton delivery (not after multiple birth).
Who cannot join
- Infant had any other condition that, in the opinion of the site investigator or designee, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives; for example, severe congenital malformation, other medical condition, or clinically significant finding from physical examination.
- At entry, any positive infant HIV nucleic acid test result (results are not required to be available prior to entry but any positive results obtained prior to entry are exclusionary).
- At entry, infant or breastfeeding mother was receiving any disallowed medication listed in the protocol.
- Mother received maraviroc during pregnancy.
Trial locations and contacts
9 sites in 4 countries.
9 sites in 4 countries
United States5 sites
Univ. of Colorado Denver NICHD CRS
Aurora, Colorado, 80045
Rush Univ. Cook County Hosp. Chicago NICHD CRS
Chicago, Illinois, 60612
Lurie Children's Hospital of Chicago (LCH) CRS
Chicago, Illinois, 60614-3393
Usc La Nichd Crs
Los Angeles, California, 90089
St. Jude Children's Research Hospital CRS
Memphis, Tennessee, 38105-3678
South Africa2 sites
Umlazi CRS
Durban, KwaZulu-Natal, 4001
Soweto IMPAACT CRS
Johannesburg, Gauteng, 1862
Kenya1 site
Kenya Medical Research Institute / Walter Reed Project Clinical Research Center, Kericho CRS
Kericho, 20200
Thailand1 site
Siriraj Hospital ,Mahidol University NICHD CRS
Bangkok, Bangkoknoi, 10700
About this study
Official title: Phase I Safety and Pharmacokinetic Study of Maraviroc in HIV-1-Exposed Infants at Risk of Acquiring HIV-1 Infection
This study aimed to evaluate the safety, tolerability, and pharmacokinetics of maraviroc in infants at risk for mother-to-child HIV transmission, and to determine an appropriate dose of maraviroc during the first six weeks of life.
Read the detailed description
Maraviroc is a C-C Chemokine Receptor 5 (CCR5) receptor antagonist used to treat HIV infection in adults. Adding maraviroc to a standard of care prophylaxis regimen may also reduce the risk of perinatal transmission of HIV. The purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics of maraviroc in HIV-1-exposed infants at risk for mother-to-child HIV transmission. This study also aimed to determine an appropriate dose of maraviroc during the first six weeks of life.
The study allowed up to 72 mother-infant pairs in two cohorts to achieve a target of 36 evaluable infants receiving the final recommended dose of maraviroc. Because maraviroc interacts with the antiretroviral drug efavirenz (EFV) in adults, infants in this study were stratified within the cohorts based on their exposure to maternal EFV. Cohort 1 was stratified by in utero exposure to maternal EFV, with infants in both strata receiving a single dose of maraviroc solution within three days of birth and another single dose at Week 1 of life. Stratum 1A included infants without in utero exposure to maternal EFV during the eight weeks immediately before delivery. Stratum 1B included infants with in utero exposure to maternal EFV for a minimum of two weeks immediately before delivery.
Cohort 2 was stratified by exposure to maternal EFV after birth, with infants in both strata receiving maraviroc oral solution twice daily starting within three days of birth and continuing for up to 42 days. Based on evaluation of the Cohort 1 data, the initial daily dose of maraviroc oral solution to be administered in Cohort 2 was 8 mg/kg dose given twice daily. Stratum 2A included infants without any exposure to maternal EFV either in utero during the eight weeks immediately before delivery or while breastfeeding. Stratum 2B included breastfeeding infants with exposure to maternal EFV both in utero and after birth while breastfeeding, for a minimum of 2 weeks immediately before delivery and while breastfeeding.
Participants attended an entry visit within three days after the infant's birth. Participants attended five to six study visits through Week 16. Visits included medical history reviews, physical examinations, blood collection from the mother and/or infant, HIV testing, and adherence counseling.
- Conditions
- HIV Infections
- Being tested
- Maraviroc
- Keywords
- Vertical HIV exposure, Neonates, Maraviroc
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MaravirocDrug
8 mg/kg oral solution as a single dose.
MaravirocDrug
8 mg/kg oral solution given twice daily.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 Stratum 1A | Experimental | Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz. Receives: Drug: Maraviroc |
| Cohort 1 Stratum 1B | Experimental | Infants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz. Receives: Drug: Maraviroc |
| Cohort 2 Stratum 2A | Experimental | Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz. Receives: Drug: Maraviroc |
| Cohort 2 Stratum 2B | Experimental | Infants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz Receives: Drug: Maraviroc |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Dose-Finding
Percentage (%) of failure and Clopper-Pearson 95% Confidence Interval (CI). Failure is defined as having: Any life threatening adverse event (AE), including death, assessed as at least possibly related to the study drug, AEs of Grade 3 or higher judged by the Core Protocol Team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an AE, judged by Core Protocol Team to be at least possibly related to study drug
Measured: Cohort 1: Measured from first dose of maraviroc to 7 Day Post Dose Visit (up to 25 days). Cohort 2: Measured from first dose of maraviroc to Week 6 Visit (up to 42 days).
Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Analysis
Percentage (%) of failure and Clopper-Pearson 95% CI. Failure is defined as: Any life threatening AE, including death, assessed as at least possibly related to the study drug, AEs of Grade 3 or higher judged by the Core Protocol Team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an AE, judged by Core Protocol Team to be at least possibly related to study drug
Measured: Measured from first dose of maraviroc to Week 6 Visit (up to 42 days)
Number of Participants Failing to Meet PK Target
Number of failures. The pharmacokinetic (PK) target is Average Concentration (Cavg) greater than or equal to 75 ng/mL (based on a dose interval of every 12 hours). Failure is defined as Cavg <75 ng/mL at each intensive PK visit.
For Cohort 1:
For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose.
For Cohort 2:
For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.
Measured: Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).
Pharmacokinetic (PK) Parameter: Average Concentration (Cavg)
Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (Phoenix 64, WinNonlin, Pharsight Corp., Mountain View, CA). Cavg was determined as the area-under-the-curve (AUC) divided by the dose interval, tau (τ) of every 12 hours.
For Cohort 1:
For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose.
For Cohort 2:
For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.
Measured: Cohort 1: Measured at Entry and Week 1 Visit. Cohort 2: Measured at Week 1 and Week 4 Visit
Pharmacokinetic (PK) Parameter: Area-under-the-curve (AUC)
Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (Phoenix 64, WinNonlin, Pharsight Corp., Mountain View, CA). For Cohort 1 (single doses), area-under-the-curve (AUC) was determined from time zero to infinity. For Cohort 2 (at steady-state), area-under-the-curve (AUC) was determined from time pre-dose to tau (12 hours).
For Cohort 1:
For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose.
For Cohort 2:
For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.
Measured: Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).
Pharmacokinetic (PK) Parameter: Maximum Concentration (Cmax)
Pharmacokinetic parameters were determined from plasma concentration-time profiles. Cmax was the observed highest concentration.
For Cohort 1:
For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose.
For Cohort 2:
For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.
Measured: Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).
Pharmacokinetic (PK) Parameter: Time of Maximum Concentration (Tmax)
Pharmacokinetic parameters were determined from plasma concentration-time profiles. Tmax was the time at which Cmax, the observed highest concentration, occurred.
For Cohort 1:
For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose.
For Cohort 2:
For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.
Measured: Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).
Pharmacokinetic (PK) Parameter: Trough Concentration (Ctau)
Pharmacokinetic parameters were determined from plasma concentration-time profiles. Ctau was the observed concentration at the trough time of 12 hours post-dose with steady-state dosing.
For Cohort 2:
For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.
Measured: Measured at Week 1 and Week 4 Visit
Secondary outcomes (2)
Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Dose-Finding
Percentage (%) of failure and Clopper-Pearson 95% CI. Failure is defined as having: Any life threatening AE, including death, assessed as at least possibly related to the study drug, AEs of Grade 3 or higher judged by the Core Protocol Team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an AE, judged by Core Protocol Team to be at least possibly related to study drug
Measured: Measured from first dose of maraviroc to Week 16 Visit (up to 140 days)
Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Analysis
Percentage (%) of failure and Clopper-Pearson 95% CI. Failure is defined as having: Any life threatening AE, including death, assessed as at least possibly related to the study drug, AEs of Grade 3 or higher judged by the Core Protocol Team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an AE, judged by Core Protocol Team to be at least possibly related to study drug
Measured: Measured from first dose of maraviroc to Week 16 Visit (up to 140 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2016 (estimated)
- Study start5 Jun 2017
- Primary completion6 Sep 2019
- Study completion20 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), ViiV Healthcare, GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Mark Mirochnick, MD, Study chair, Boston University School of Medicine/Boston Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02778204
- Sponsor's protocol ID
- IMPAACT 2007
- Other IDs
- 20734
- Status last verified
- Dec 2021
- First submitted
- 13 May 2016
- Last updated
- 4 Jan 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Safety and Pharmacokinetic Study of Maraviroc in HIV-1-Exposed Infants at Risk of Acquiring HIV-1 Infection
- ClinicalTrials.gov ID
- NCT02778204
- Acronym / sponsor ID
- IMPAACT 2007
- Conditions
- HIV Infections
- Keywords
- Vertical HIV exposure, Neonates, Maraviroc
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 47 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), ViiV Healthcare, GlaxoSmithKline
- Study start
- 5 Jun 2017 (actual)
- Primary completion
- 6 Sep 2019 (actual)
- Study completion
- 20 Nov 2019 (actual)
- First posted
- 19 May 2016 (estimated)
- Results
- Posted 23 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aimed to evaluate the safety, tolerability, and pharmacokinetics of maraviroc in infants at risk for mother-to-child HIV transmission, and to determine an appropriate dose of maraviroc during the first six weeks of life.
Detailed description
Maraviroc is a C-C Chemokine Receptor 5 (CCR5) receptor antagonist used to treat HIV infection in adults. Adding maraviroc to a standard of care prophylaxis regimen may also reduce the risk of perinatal transmission of HIV. The purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics of maraviroc in HIV-1-exposed infants at risk for mother-to-child HIV transmission. This study also aimed to determine an appropriate dose of maraviroc during the first six weeks of life.
The study allowed up to 72 mother-infant pairs in two cohorts to achieve a target of 36 evaluable infants receiving the final recommended dose of maraviroc. Because maraviroc interacts with the antiretroviral drug efavirenz (EFV) in adults, infants in this study were stratified within the cohorts based on their exposure to maternal EFV. Cohort 1 was stratified by in utero exposure to maternal EFV, with infants in both strata receiving a single dose of maraviroc solution within three days of birth and another single dose at Week 1 of life. Stratum 1A included infants without in utero exposure to maternal EFV during the eight weeks immediately before delivery. Stratum 1B included infants with in utero exposure to maternal EFV for a minimum of two weeks immediately before delivery.
Cohort 2 was stratified by exposure to maternal EFV after birth, with infants in both strata receiving maraviroc oral solution twice daily starting within three days of birth and continuing for up to 42 days. Based on evaluation of the Cohort 1 data, the initial daily dose of maraviroc oral solution to be administered in Cohort 2 was 8 mg/kg dose given twice daily. Stratum 2A included infants without any exposure to maternal EFV either in utero during the eight weeks immediately before delivery or while breastfeeding. Stratum 2B included breastfeeding infants with exposure to maternal EFV both in utero and after birth while breastfeeding, for a minimum of 2 weeks immediately before delivery and while breastfeeding.
Participants attended an entry visit within three days after the infant's birth. Participants attended five to six study visits through Week 16. Visits included medical history reviews, physical examinations, blood collection from the mother and/or infant, HIV testing, and adherence counseling.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 Stratum 1A | Experimental | Drug: MaravirocInfants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; without in utero exposure to maternal efavirenz. |
| Cohort 1 Stratum 1B | Experimental | Drug: MaravirocInfants in this cohort received a single dose of 8 mg/kg maraviroc solution within 3 days of birth and at Week 1 (7-14 days) of life; with in utero exposure to maternal efavirenz. |
| Cohort 2 Stratum 2A | Experimental | Drug: MaravirocInfants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; without in utero or breast milk exposure to maternal efavirenz. |
| Cohort 2 Stratum 2B | Experimental | Drug: MaravirocInfants in this cohort received 8 mg/kg maraviroc solution twice daily starting within 3 days of birth and continuing up to Week 6 (35-42) days of life; with in utero and breast milk exposure to maternal efavirenz |
Who may qualify
- Ages
- Up to 3 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (17 listed)
- Mother was of legal age to provide independent informed consent for research participation and was willing and able to provide written informed consent for her and her infant's participation in this study.
- Mother had confirmed HIV-1 infection based on testing of two samples collected at different time points. More information on this criterion can be found in the protocol.
- At entry, infant met EFV exposure requirements, based on mother's report and confirmed by medical records if available, as follows:
- At birth, infant's estimated gestational age was at least 37 weeks. Note: If gestational age at birth is not documented in the infant's available birth records, study staff may assess gestational age at the earliest possible opportunity during the screening period and use this assessment for purposes of eligibility determination.
- At birth, infant's weight was at least 2 kg. Note: If weight at birth is not documented in the infant's available birth records, study staff may assess infant weight at the earliest possible opportunity during the screening period and use this assessment for purposes of eligibility determination.
Key exclusion criteria (4 listed)
- Infant had any other condition that, in the opinion of the site investigator or designee, would make participation in the study unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives; for example, severe congenital malformation, other medical condition, or clinically significant finding from physical examination.
- At entry, any positive infant HIV nucleic acid test result (results are not required to be available prior to entry but any positive results obtained prior to entry are exclusionary).
- At entry, infant or breastfeeding mother was receiving any disallowed medication listed in the protocol.
- Mother received maraviroc during pregnancy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Maraviroc8 mg/kg oral solution as a single dose. | Drug | Cohort 1 Stratum 1A, Cohort 1 Stratum 1B |
| Maraviroc8 mg/kg oral solution given twice daily. | Drug | Cohort 2 Stratum 2A, Cohort 2 Stratum 2B |
Primary outcome
Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Dose-Finding
Time frame: Cohort 1: Measured from first dose of maraviroc to 7 Day Post Dose Visit (up to 25 days). Cohort 2: Measured from first dose of maraviroc to Week 6 Visit (up to 42 days).
Percentage (%) of failure and Clopper-Pearson 95% Confidence Interval (CI). Failure is defined as having: Any life threatening adverse event (AE), including death, assessed as at least possibly related to the study drug, AEs of Grade 3 or higher judged by the Core Protocol Team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an AE, judged by Core Protocol Team to be at least possibly related to study drug
Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Analysis
Time frame: Measured from first dose of maraviroc to Week 6 Visit (up to 42 days)
Percentage (%) of failure and Clopper-Pearson 95% CI. Failure is defined as: Any life threatening AE, including death, assessed as at least possibly related to the study drug, AEs of Grade 3 or higher judged by the Core Protocol Team to be probably or definitely related to the study drug, or that result in permanent discontinuation of study drug due to an AE, judged by Core Protocol Team to be at least possibly related to study drug
Number of Participants Failing to Meet PK Target
Time frame: Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).
Number of failures. The pharmacokinetic (PK) target is Average Concentration (Cavg) greater than or equal to 75 ng/mL (based on a dose interval of every 12 hours). Failure is defined as Cavg <75 ng/mL at each intensive PK visit. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.
Pharmacokinetic (PK) Parameter: Average Concentration (Cavg)
Time frame: Cohort 1: Measured at Entry and Week 1 Visit. Cohort 2: Measured at Week 1 and Week 4 Visit
Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (Phoenix 64, WinNonlin, Pharsight Corp., Mountain View, CA). Cavg was determined as the area-under-the-curve (AUC) divided by the dose interval, tau (τ) of every 12 hours. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.
Pharmacokinetic (PK) Parameter: Area-under-the-curve (AUC)
Time frame: Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).
Pharmacokinetic parameters were determined from plasma concentration-time profiles using non-compartmental methods (Phoenix 64, WinNonlin, Pharsight Corp., Mountain View, CA). For Cohort 1 (single doses), area-under-the-curve (AUC) was determined from time zero to infinity. For Cohort 2 (at steady-state), area-under-the-curve (AUC) was determined from time pre-dose to tau (12 hours). For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.
Pharmacokinetic (PK) Parameter: Maximum Concentration (Cmax)
Time frame: Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).
Pharmacokinetic parameters were determined from plasma concentration-time profiles. Cmax was the observed highest concentration. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.
Pharmacokinetic (PK) Parameter: Time of Maximum Concentration (Tmax)
Time frame: Cohort 1: Measured at Entry (First visit) and Week 1 Visit (Second visit). Cohort 2: Measured at Week 1 (First visit) and Week 4 Visit (Second visit).
Pharmacokinetic parameters were determined from plasma concentration-time profiles. Tmax was the time at which Cmax, the observed highest concentration, occurred. For Cohort 1: For the Entry Visit, PK samples were drawn at: pre-dose and at 1-2, 4-8, 11-13, 20-24, and 48-72 hours post-dose. For the Week 1 Visit, PK samples were drawn at: pre-dose and 1-2 and 22-26 hours post-dose. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.
Pharmacokinetic (PK) Parameter: Trough Concentration (Ctau)
Time frame: Measured at Week 1 and Week 4 Visit
Pharmacokinetic parameters were determined from plasma concentration-time profiles. Ctau was the observed concentration at the trough time of 12 hours post-dose with steady-state dosing. For Cohort 2: For both intensive PK visits, PK samples were drawn at: pre-dose and 1-2, 3-5, 6-8, and 11-13 hours post-dose.
2 secondary outcomes
Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Dose-Finding
Time frame: Measured from first dose of maraviroc to Week 16 Visit (up to 140 days)
Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Analysis
Time frame: Measured from first dose of maraviroc to Week 16 Visit (up to 140 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jan 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark Mirochnick, MD study chair
Boston University School of Medicine/Boston Medical Center
9 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Maraviroc in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 9 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, South Africa, Kenya, Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Dose-Finding (time frame: Cohort 1: Measured from first dose of maraviroc to 7 Day Post Dose Visit (up to 25 days). Cohort 2: Measured from first dose of maraviroc to Week 6 Visit (up to 42 days).). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jan 2022.