Evaluating the Safety and Pharmacokinetics of Maraviroc in HIV-1-Exposed Infants at Risk of Acquiring HIV-1 Infection
Study Details
Study Description
Brief 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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
Phase 1 |
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
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Cohort 1 Stratum 1A 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. |
Drug: Maraviroc
8 mg/kg oral solution as a single dose.
|
Experimental: Cohort 1 Stratum 1B 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. |
Drug: Maraviroc
8 mg/kg oral solution as a single dose.
|
Experimental: Cohort 2 Stratum 2A 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. |
Drug: Maraviroc
8 mg/kg oral solution given twice daily.
|
Experimental: Cohort 2 Stratum 2B 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 |
Drug: Maraviroc
8 mg/kg oral solution given twice daily.
|
Outcome Measures
Primary Outcome Measures
- Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Dose-Finding [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 [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 [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) [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) [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) [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) [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) [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.
Secondary Outcome Measures
- Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Dose-Finding [Measured from first dose of maraviroc to Week 16 Visit (up to 140 days)]
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
- Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Analysis [Measured from first dose of maraviroc to Week 16 Visit (up to 140 days)]
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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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.
-
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).
Exclusion Criteria:
-
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.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Usc La Nichd Crs | Los Angeles | California | United States | 90089 |
2 | Univ. of Colorado Denver NICHD CRS | Aurora | Colorado | United States | 80045 |
3 | Rush Univ. Cook County Hosp. Chicago NICHD CRS | Chicago | Illinois | United States | 60612 |
4 | Lurie Children's Hospital of Chicago (LCH) CRS | Chicago | Illinois | United States | 60614-3393 |
5 | St. Jude Children's Research Hospital CRS | Memphis | Tennessee | United States | 38105-3678 |
6 | Kenya Medical Research Institute / Walter Reed Project Clinical Research Center, Kericho CRS | Kericho | Kenya | 20200 | |
7 | Soweto IMPAACT CRS | Johannesburg | Gauteng | South Africa | 1862 |
8 | Umlazi CRS | Durban | Kwa Zulu Natal | South Africa | 4001 |
9 | Siriraj Hospital ,Mahidol University NICHD CRS | Bangkok | Bangkoknoi | Thailand | 10700 |
Sponsors and Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- ViiV Healthcare
- GlaxoSmithKline
Investigators
- Study Chair: Mark Mirochnick, MD, Boston University School of Medicine/Boston Medical Center
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.- IMPAACT 2007
- 20734
Study Results
Participant Flow
Recruitment Details | Accrual occurred between June 2017 and July 2019 in Kenya, Thailand, South Africa, and the United States at 9 different medical clinic sites. Pregnant mothers were screened and subsequently enrolled for 1 day at the same day their newborn infants were enrolled (within 3 days of life). |
---|---|
Pre-assignment Detail | The sample size of the study (47) represents the infants enrolled. As multiple births are disallowed in the study, this also represents the total mother-infant pairs. |
Arm/Group Title | Cohort 1 Stratum 1A | Cohort 1 Stratum 1B | Cohort 2 Stratum 2A | Cohort 2 Stratum 2B |
---|---|---|---|---|
Arm/Group Description | 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. | 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. | 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. | 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 |
Period Title: Overall Study | ||||
STARTED | 8 | 7 | 16 | 16 |
COMPLETED | 6 | 7 | 12 | 12 |
NOT COMPLETED | 2 | 0 | 4 | 4 |
Baseline Characteristics
Arm/Group Title | Cohort 1 Stratum 1A | Cohort 1 Stratum 1B | Cohort 2 Stratum 2A | Cohort 2 Stratum 2B | Total |
---|---|---|---|---|---|
Arm/Group Description | 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. | 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. | 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. | 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 | Total of all reporting groups |
Overall Participants | 8 | 7 | 16 | 16 | 47 |
Age (days) [Median (Inter-Quartile Range) ] | |||||
Mean (Standard Deviation) |
1.5
|
0
|
1
|
2
|
2
|
Age (years) [Median (Inter-Quartile Range) ] | |||||
Median (Inter-Quartile Range) [years] |
29.5
|
26
|
32
|
32
|
31
|
Sex: Female, Male (Count of Participants) | |||||
Female |
5
62.5%
|
4
57.1%
|
7
43.8%
|
7
43.8%
|
23
48.9%
|
Male |
3
37.5%
|
3
42.9%
|
9
56.3%
|
9
56.3%
|
24
51.1%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||||
Hispanic or Latino |
3
37.5%
|
0
0%
|
2
12.5%
|
0
0%
|
5
10.6%
|
Not Hispanic or Latino |
5
62.5%
|
7
100%
|
14
87.5%
|
16
100%
|
42
89.4%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | |||||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
0
0%
|
3
18.8%
|
0
0%
|
3
6.4%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Black or African American |
5
62.5%
|
7
100%
|
10
62.5%
|
16
100%
|
38
80.9%
|
White |
3
37.5%
|
0
0%
|
3
18.8%
|
0
0%
|
6
12.8%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Region of Enrollment (participants) [Number] | |||||
United States |
7
87.5%
|
0
0%
|
13
81.3%
|
0
0%
|
20
42.6%
|
South Africa |
1
12.5%
|
7
100%
|
0
0%
|
14
87.5%
|
22
46.8%
|
Thailand |
0
0%
|
0
0%
|
3
18.8%
|
0
0%
|
3
6.4%
|
Kenya |
0
0%
|
0
0%
|
0
0%
|
2
12.5%
|
2
4.3%
|
Birth Weight (kilograms) [Median (Inter-Quartile Range) ] | |||||
Median (Inter-Quartile Range) [kilograms] |
3.2
|
3.4
|
3.0
|
3.0
|
3.05
|
Birth Length (centimeters) [Median (Inter-Quartile Range) ] | |||||
Median (Inter-Quartile Range) [centimeters] |
50.0
|
50.0
|
49.0
|
48.5
|
49.0
|
Gestational Age (weeks) [Median (Inter-Quartile Range) ] | |||||
Median (Inter-Quartile Range) [weeks] |
38.5
|
39.0
|
39.0
|
40.0
|
39.0
|
APGAR at 1 minute (units on a scale) [Median (Inter-Quartile Range) ] | |||||
Median (Inter-Quartile Range) [units on a scale] |
9.0
|
8.0
|
8.5
|
9.0
|
9.0
|
Alanine Aminotransferase (ALT) (ukat/L) [Median (Inter-Quartile Range) ] | |||||
Median (Inter-Quartile Range) [ukat/L] |
0.2
|
0.2
|
0.2
|
0.2
|
0.2
|
Aspartate Aminotransferase (AST) (ukat/L) [Median (Inter-Quartile Range) ] | |||||
Median (Inter-Quartile Range) [ukat/L] |
0.7
|
1.1
|
0.9
|
1.0
|
0.9
|
Total Bilirubin (umol/L) [Median (Inter-Quartile Range) ] | |||||
Median (Inter-Quartile Range) [umol/L] |
39.3
|
44.0
|
76.1
|
75.3
|
50.7
|
Creatinine (umol/L) [Median (Inter-Quartile Range) ] | |||||
Median (Inter-Quartile Range) [umol/L] |
70.7
|
62.0
|
61.9
|
69.0
|
66
|
Platelets (10^9 platelets/L) [Median (Inter-Quartile Range) ] | |||||
Median (Inter-Quartile Range) [10^9 platelets/L] |
274.0
|
297.0
|
252.5
|
311.0
|
289.0
|
Hemoglobin (g/L) [Median (Inter-Quartile Range) ] | |||||
Median (Inter-Quartile Range) [g/L] |
163.0
|
178.0
|
166.5
|
179.0
|
170.0
|
White Blood Cell Count (WBC) (10^9 cells/L) [Median (Inter-Quartile Range) ] | |||||
Median (Inter-Quartile Range) [10^9 cells/L] |
14.6
|
17.3
|
15.5
|
12.6
|
14.6
|
Outcome Measures
Title | Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Dose-Finding |
---|---|
Description | 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 |
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). |
Outcome Measure Data
Analysis Population Description |
---|
Safety-evaluable population are those who were taking maraviroc for the expected time-frame (Cohort 1: through 7 day post-dose visit, Cohort 2: Through week 6) |
Arm/Group Title | Cohort 1 Stratum 1A | Cohort 1 Stratum 1B | Cohort 2 Stratum 2A | Cohort 2 Stratum 2B |
---|---|---|---|---|
Arm/Group Description | 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. | 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. | 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. | 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 |
Measure Participants | 6 | 7 | 12 | 12 |
Number (95% Confidence Interval) [percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Title | Percentage of Participants Failing to Meet Safety Endpoint Related to Maraviroc for Analysis |
---|---|
Description | 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 |
Time Frame | Measured from first dose of maraviroc to Week 6 Visit (up to 42 days) |
Outcome Measure Data
Analysis Population Description |
---|
Analysis Endpoint includes all treated participants |
Arm/Group Title | Cohort 1 Stratum 1A | Cohort 1 Stratum 1B | Cohort 2 Stratum 2A | Cohort 2 Stratum 2B |
---|---|---|---|---|
Arm/Group Description | 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. | 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. | 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. | 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 |
Measure Participants | 8 | 7 | 16 | 16 |
Number (95% Confidence Interval) [percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Title | Number of Participants Failing to Meet PK Target |
---|---|
Description | 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. |
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). |
Outcome Measure Data
Analysis Population Description |
---|
Analysis population included dose-finding evaluable participants with intensive pharmacokinetic (PK) results. In Cohort 1 Stratum 1A and 1B at the week 1 visit (Second Visit), only 3 PK sample were drawn (pre-dose, 1-2 hours post-dose, and 22-26 hours post-dose). Maraviroc was only measurable (above assay limit) at 1 time point (1-2 hours post-dose). Therefore, AUC (hence Cavg) could not be estimated with non-compartmental methods from only 1 concentration and thus the number analyzed was 0. |
Arm/Group Title | Cohort 1 Stratum 1A | Cohort 1 Stratum 1B | Cohort 2 Stratum 2A | Cohort 2 Stratum 2B |
---|---|---|---|---|
Arm/Group Description | 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. | 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. | 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. | 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 |
Measure Participants | 6 | 7 | 13 | 12 |
First Visit |
0
0%
|
0
0%
|
3
18.8%
|
4
25%
|
Second Visit |
4
50%
|
5
71.4%
|
Title | Pharmacokinetic (PK) Parameter: Average Concentration (Cavg) |
---|---|
Description | 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. |
Time Frame | Cohort 1: Measured at Entry and Week 1 Visit. Cohort 2: Measured at Week 1 and Week 4 Visit |
Outcome Measure Data
Analysis Population Description |
---|
Analysis population included dose-finding evaluable participants with intensive pharmacokinetic (PK) results. In Cohort 1 Stratum 1A and 1B at the week 1 visit (Second Visit), only 3 PK sample were drawn (pre-dose, 1-2 hours post-dose, and 22-26 hours post-dose). Maraviroc was only measurable (above assay limit) at 1 time point (1-2 hours post-dose). Therefore, AUC (hence Cavg) could not be estimated with non-compartmental methods from only 1 concentration and thus the number analyzed was 0. |
Arm/Group Title | Cohort 1 Stratum 1A | Cohort 1 Stratum 1B | Cohort 2 Stratum 2A | Cohort 2 Stratum 2B |
---|---|---|---|---|
Arm/Group Description | 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. | 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. | 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. | 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 |
Measure Participants | 6 | 7 | 13 | 12 |
First Visit |
190.47
|
375.47
|
152.24
|
124.67
|
Second Visit |
93.58
|
101.39
|
Title | Pharmacokinetic (PK) Parameter: Area-under-the-curve (AUC) |
---|---|
Description | 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. |
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). |
Outcome Measure Data
Analysis Population Description |
---|
Analysis population included dose-finding evaluable participants with intensive pharmacokinetic (PK) results. In Cohort 1 Stratum 1A and 1B at the week 1 visit (Second Visit), only 3 PK sample were drawn (pre-dose, 1-2 hours post-dose, and 22-26 hours post-dose). Maraviroc was only measurable (above assay limit) at 1 time point (1-2 hours post-dose). Therefore, AUC (hence Cavg) could not be estimated with non-compartmental methods from only 1 concentration and thus the number analyzed was 0. |
Arm/Group Title | Cohort 1 Stratum 1A | Cohort 1 Stratum 1B | Cohort 2 Stratum 2A | Cohort 2 Stratum 2B |
---|---|---|---|---|
Arm/Group Description | 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. | 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. | 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. | 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 |
Measure Participants | 6 | 7 | 13 | 12 |
First Visit |
2285.68
|
4506.17
|
1826.87
|
1496.05
|
Second Visit |
1122.99
|
1216.62
|
Title | Pharmacokinetic (PK) Parameter: Maximum Concentration (Cmax) |
---|---|
Description | 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. |
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). |
Outcome Measure Data
Analysis Population Description |
---|
Analysis population included dose-finding evaluable participants with intensive pharmacokinetic (PK) results. |
Arm/Group Title | Cohort 1 Stratum 1A | Cohort 1 Stratum 1B | Cohort 2 Stratum 2A | Cohort 2 Stratum 2B |
---|---|---|---|---|
Arm/Group Description | 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. | 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. | 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. | 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 |
Measure Participants | 6 | 7 | 13 | 12 |
First Visit |
227.3
|
550.5
|
256.9
|
308.8
|
Second Visit |
128.9
|
163.4
|
416.5
|
221.8
|
Title | Pharmacokinetic (PK) Parameter: Time of Maximum Concentration (Tmax) |
---|---|
Description | 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. |
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). |
Outcome Measure Data
Analysis Population Description |
---|
Analysis population included dose-finding evaluable participants with intensive pharmacokinetic (PK) results. |
Arm/Group Title | Cohort 1 Stratum 1A | Cohort 1 Stratum 1B | Cohort 2 Stratum 2A | Cohort 2 Stratum 2B |
---|---|---|---|---|
Arm/Group Description | 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. | 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. | 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. | 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 |
Measure Participants | 6 | 7 | 13 | 12 |
First Visit |
4.68
|
1.52
|
1.50
|
3.00
|
Second Visit |
1.18
|
1.08
|
1.50
|
2.19
|
Title | Pharmacokinetic (PK) Parameter: Trough Concentration (Ctau) |
---|---|
Description | 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. |
Time Frame | Measured at Week 1 and Week 4 Visit |
Outcome Measure Data
Analysis Population Description |
---|
Analysis population included Cohort 2 dose-finding evaluable participants with intensive pharmacokinetic (PK) results. |
Arm/Group Title | Cohort 2 Stratum 2A | Cohort 2 Stratum 2B |
---|---|---|
Arm/Group Description | 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. | 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 |
Measure Participants | 13 | 12 |
Week 1 Visit |
27.9
|
23.4
|
Week 4 Visit |
34.4
|
54.9
|
Title | Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Dose-Finding |
---|---|
Description | 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 |
Time Frame | Measured from first dose of maraviroc to Week 16 Visit (up to 140 days) |
Outcome Measure Data
Analysis Population Description |
---|
Safety-evaluable population are those who were taking maraviroc for the expected time-frame (Cohort 1: through 7 day post-dose visit, Cohort 2: Through week 6) |
Arm/Group Title | Cohort 1 Stratum 1A | Cohort 1 Stratum 1B | Cohort 2 Stratum 2A | Cohort 2 Stratum 2B |
---|---|---|---|---|
Arm/Group Description | 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. | 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. | 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. | 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 |
Measure Participants | 6 | 7 | 12 | 12 |
Number (95% Confidence Interval) [percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Title | Percentage of Participants Failing to Meet Long-Term Safety Endpoint Related to Maraviroc for Analysis |
---|---|
Description | 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 |
Time Frame | Measured from first dose of maraviroc to Week 16 Visit (up to 140 days) |
Outcome Measure Data
Analysis Population Description |
---|
All treated participants |
Arm/Group Title | Cohort 1 Stratum 1A | Cohort 1 Stratum 1B | Cohort 2 Stratum 2A | Cohort 2 Stratum 2B |
---|---|---|---|---|
Arm/Group Description | 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. | 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. | 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. | 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 |
Measure Participants | 8 | 7 | 16 | 16 |
Number (95% Confidence Interval) [percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Adverse Events
Time Frame | From study entry to study completion at Week 16 or premature study discontinuation | |||||||
---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | All new diagnoses, signs/symptoms and laboratory events of ≥Grade 1 and all signs/symptoms and laboratory events that led to a change in treatment, regardless of grade, were collected. Adverse events (AE) were graded according to the 246 Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, dated July 2017 | |||||||
Arm/Group Title | Cohort 1 Stratum 1A | Cohort 1 Stratum 1B | Cohort 2 Stratum 2A | Cohort 2 Stratum 2B | ||||
Arm/Group Description | 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. | 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. | 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. | 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 | ||||
All Cause Mortality |
||||||||
Cohort 1 Stratum 1A | Cohort 1 Stratum 1B | Cohort 2 Stratum 2A | Cohort 2 Stratum 2B | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 0/16 (0%) | ||||
Serious Adverse Events |
||||||||
Cohort 1 Stratum 1A | Cohort 1 Stratum 1B | Cohort 2 Stratum 2A | Cohort 2 Stratum 2B | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 2/8 (25%) | 1/7 (14.3%) | 4/16 (25%) | 2/16 (12.5%) | ||||
Blood and lymphatic system disorders | ||||||||
Haemolytic anaemia | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Cardiac disorders | ||||||||
Cyanosis | 1/8 (12.5%) | 0/7 (0%) | 0/16 (0%) | 0/16 (0%) | ||||
Congenital, familial and genetic disorders | ||||||||
Hypospadias | 0/8 (0%) | 1/7 (14.3%) | 0/16 (0%) | 0/16 (0%) | ||||
Hepatobiliary disorders | ||||||||
Jaundice | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Infections and infestations | ||||||||
Escherichia urinary tract infection | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Pneumonia bacterial | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Sepsis neonatal | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Staphylococcal sepsis | 1/8 (12.5%) | 0/7 (0%) | 0/16 (0%) | 0/16 (0%) | ||||
Investigations | ||||||||
Haemoglobin decreased | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Neutrophil count decreased | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Weight decreased | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Metabolism and nutrition disorders | ||||||||
Failure to thrive | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | ||||
Nervous system disorders | ||||||||
Slow response to stimuli | 1/8 (12.5%) | 0/7 (0%) | 0/16 (0%) | 0/16 (0%) | ||||
Tremor | 1/8 (12.5%) | 0/7 (0%) | 0/16 (0%) | 0/16 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
Cohort 1 Stratum 1A | Cohort 1 Stratum 1B | Cohort 2 Stratum 2A | Cohort 2 Stratum 2B | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 7/8 (87.5%) | 7/7 (100%) | 15/16 (93.8%) | 14/16 (87.5%) | ||||
Blood and lymphatic system disorders | ||||||||
Haemolytic anaemia | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Cardiac disorders | ||||||||
Tachycardia | 0/8 (0%) | 0/7 (0%) | 2/16 (12.5%) | 0/16 (0%) | ||||
Congenital, familial and genetic disorders | ||||||||
Congenital melanocytic naevus | 1/8 (12.5%) | 0/7 (0%) | 0/16 (0%) | 0/16 (0%) | ||||
Congenital syphilis | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Hypospadias | 0/8 (0%) | 1/7 (14.3%) | 0/16 (0%) | 0/16 (0%) | ||||
Eye disorders | ||||||||
Conjunctival pallor | 0/8 (0%) | 1/7 (14.3%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Eye discharge | 1/8 (12.5%) | 1/7 (14.3%) | 0/16 (0%) | 3/16 (18.8%) | ||||
Ocular hyperaemia | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Orbital oedema | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Gastrointestinal disorders | ||||||||
Abdominal distension | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Abdominal pain | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Diarrhoea | 0/8 (0%) | 1/7 (14.3%) | 3/16 (18.8%) | 0/16 (0%) | ||||
Infantile colic | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Infantile vomiting | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Mouth ulceration | 0/8 (0%) | 1/7 (14.3%) | 0/16 (0%) | 0/16 (0%) | ||||
Teething | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
General disorders | ||||||||
Face oedema | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Feeling hot | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 2/16 (12.5%) | ||||
Pyrexia | 0/8 (0%) | 1/7 (14.3%) | 2/16 (12.5%) | 1/16 (6.3%) | ||||
Hepatobiliary disorders | ||||||||
Hyperbilirubinaemia | 0/8 (0%) | 0/7 (0%) | 2/16 (12.5%) | 0/16 (0%) | ||||
Hyperbilirubinaemia neonatal | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Jaundice | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Infections and infestations | ||||||||
Acarodermatitis | 0/8 (0%) | 1/7 (14.3%) | 0/16 (0%) | 0/16 (0%) | ||||
Conjunctivitis bacterial | 1/8 (12.5%) | 0/7 (0%) | 0/16 (0%) | 0/16 (0%) | ||||
Escherichia urinary tract infection | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Genital candidiasis | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Impetigo | 0/8 (0%) | 2/7 (28.6%) | 0/16 (0%) | 0/16 (0%) | ||||
Nasopharyngitis | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Ophthalmia neonatorum | 1/8 (12.5%) | 0/7 (0%) | 1/16 (6.3%) | 2/16 (12.5%) | ||||
Oral candidiasis | 1/8 (12.5%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Pneumonia bacterial | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | ||||
Sepsis neonatal | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Staphylococcal sepsis | 1/8 (12.5%) | 0/7 (0%) | 0/16 (0%) | 0/16 (0%) | ||||
Tinea versicolour | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Injury, poisoning and procedural complications | ||||||||
Contusion | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Eyelid injury | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Investigations | ||||||||
Alanine aminotransferase increased | 0/8 (0%) | 1/7 (14.3%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Aspartate aminotransferase increased | 1/8 (12.5%) | 0/7 (0%) | 0/16 (0%) | 3/16 (18.8%) | ||||
Bilirubin conjugated increased | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Blood bilirubin increased | 2/8 (25%) | 0/7 (0%) | 9/16 (56.3%) | 4/16 (25%) | ||||
Blood potassium increased | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Cardiac murmur | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Haemoglobin decreased | 4/8 (50%) | 4/7 (57.1%) | 11/16 (68.8%) | 5/16 (31.3%) | ||||
Neutrophil count decreased | 0/8 (0%) | 2/7 (28.6%) | 5/16 (31.3%) | 7/16 (43.8%) | ||||
Weight decreased | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 1/16 (6.3%) | ||||
White blood cell count decreased | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Metabolism and nutrition disorders | ||||||||
Failure to thrive | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 1/16 (6.3%) | ||||
Hyperkalaemia | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Malnutrition | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Poor feeding infant | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Underweight | 3/8 (37.5%) | 1/7 (14.3%) | 4/16 (25%) | 0/16 (0%) | ||||
Musculoskeletal and connective tissue disorders | ||||||||
Acquired macrocephaly | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Nervous system disorders | ||||||||
Hypertonia | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Hypotonia | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Pregnancy, puerperium and perinatal conditions | ||||||||
Jaundice neonatal | 1/8 (12.5%) | 0/7 (0%) | 3/16 (18.8%) | 2/16 (12.5%) | ||||
Small for dates baby | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Psychiatric disorders | ||||||||
Irritability | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Respiratory, thoracic and mediastinal disorders | ||||||||
Cough | 0/8 (0%) | 1/7 (14.3%) | 2/16 (12.5%) | 4/16 (25%) | ||||
Hypoxia | 0/8 (0%) | 0/7 (0%) | 2/16 (12.5%) | 0/16 (0%) | ||||
Nasal congestion | 0/8 (0%) | 3/7 (42.9%) | 2/16 (12.5%) | 3/16 (18.8%) | ||||
Neonatal hypoxia | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Rhinorrhoea | 0/8 (0%) | 0/7 (0%) | 2/16 (12.5%) | 2/16 (12.5%) | ||||
Sneezing | 0/8 (0%) | 0/7 (0%) | 2/16 (12.5%) | 0/16 (0%) | ||||
Tachypnoea | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Use of accessory respiratory muscles | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Skin and subcutaneous tissue disorders | ||||||||
Dermatitis diaper | 1/8 (12.5%) | 2/7 (28.6%) | 0/16 (0%) | 2/16 (12.5%) | ||||
Erythema toxicum neonatorum | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Intertrigo | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Miliaria | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 2/16 (12.5%) | ||||
Papule | 0/8 (0%) | 2/7 (28.6%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Petechiae | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Pruritus | 0/8 (0%) | 0/7 (0%) | 0/16 (0%) | 1/16 (6.3%) | ||||
Rash | 1/8 (12.5%) | 5/7 (71.4%) | 1/16 (6.3%) | 3/16 (18.8%) | ||||
Rash neonatal | 0/8 (0%) | 2/7 (28.6%) | 1/16 (6.3%) | 3/16 (18.8%) | ||||
Rash papular | 1/8 (12.5%) | 0/7 (0%) | 0/16 (0%) | 0/16 (0%) | ||||
Seborrhoeic dermatitis | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) | ||||
Vascular disorders | ||||||||
Haematoma | 0/8 (0%) | 0/7 (0%) | 1/16 (6.3%) | 0/16 (0%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights
Results Point of Contact
Name/Title | Melissa Allen, Director, IMPAACT Operations Center |
---|---|
Organization | Family Health International (FHI 360) |
Phone | (919) 405-1429 |
mallen@fhi360.org |
- IMPAACT 2007
- 20734