Trial Outcomes & Findings for TMC125-TiDP35-C213: Safety and Antiviral Activity of Etravirine (TMC125) in Treatment-Experienced, HIV Infected Children and Adolescents (NCT NCT00665847)
NCT ID: NCT00665847
Last Updated: 2015-04-23
Results Overview
A treatment-emergent adverse event (TEAE) was defined as an event that occurred in the 48-week treatment period during which it emerged (i.e. started or worsened in severity, relation, or other attribute), and not in the subsequent study periods, even if the event continued to be present. Adverse events were graded from 1 to 4 in severity using the Division of Acquired Immunodeficiency Syndrome severity scale (grade 1 being less severe and grade 4 being more severe). ETR=etravirine/TMC125; OBR=optimized background regimen
COMPLETED
PHASE2
103 participants
48 weeks
2015-04-23
Participant Flow
In total, 41 investigators in 13 countries enrolled patients in study TMC125-C213. A total of 103 patients were documented as being enrolled in the study, however 2 patients were randomized in error. Therefore, 101 patients were enrolled and treated with etravirine (ETR) also known as TMC125 and included in the intent-to-treat (ITT) population.
Participant milestones
| Measure |
TMC125
TMC125 dosed according to body weight (kg) from 100 mg to 200 mg twice a day
|
|---|---|
|
Overall Study
STARTED
|
101
|
|
Overall Study
COMPLETED
|
76
|
|
Overall Study
NOT COMPLETED
|
25
|
Reasons for withdrawal
| Measure |
TMC125
TMC125 dosed according to body weight (kg) from 100 mg to 200 mg twice a day
|
|---|---|
|
Overall Study
Adverse Event
|
8
|
|
Overall Study
Withdrawal by Subject
|
2
|
|
Overall Study
Subject non-compliant
|
8
|
|
Overall Study
Subject reached a virologic endpoint
|
4
|
|
Overall Study
Resistance to TMC125
|
1
|
|
Overall Study
Subject ineligible to continue the trial
|
1
|
|
Overall Study
Switch to Commercial Medication
|
1
|
Baseline Characteristics
TMC125-TiDP35-C213: Safety and Antiviral Activity of Etravirine (TMC125) in Treatment-Experienced, HIV Infected Children and Adolescents
Baseline characteristics by cohort
| Measure |
TMC125
n=101 Participants
TMC125 dosed according to body weight (kg) from 100 mg to 200 mg twice a day
|
|---|---|
|
Age, Continuous
|
12.2 years
STANDARD_DEVIATION 2.99 • n=5 Participants
|
|
Sex: Female, Male
Female
|
64 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
37 Participants
n=5 Participants
|
|
Age Customized
>=6 to <12 years
|
41 participants
n=5 Participants
|
|
Age Customized
>=12 to <18 years
|
60 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 48 weeksPopulation: The safety analysis was done on the intent-to-treat (ITT) population, which included all patients who received at least one dose of investigational medication.
A treatment-emergent adverse event (TEAE) was defined as an event that occurred in the 48-week treatment period during which it emerged (i.e. started or worsened in severity, relation, or other attribute), and not in the subsequent study periods, even if the event continued to be present. Adverse events were graded from 1 to 4 in severity using the Division of Acquired Immunodeficiency Syndrome severity scale (grade 1 being less severe and grade 4 being more severe). ETR=etravirine/TMC125; OBR=optimized background regimen
Outcome measures
| Measure |
TMC125
n=101 Participants
TMC125 dosed based on body weight (kg) from 100 mg to 200 mg twice a day
|
|---|---|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs that were grade 3 or 4 in severity
|
14 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: Rash
|
23 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: hepatic events
|
0 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: cardiac events
|
0 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: bleeding events
|
0 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: pancreatic events
|
1 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: lipid-related events
|
6 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: neoplasms
|
1 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
Any TEAE
|
89 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs that were fatal
|
0 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs that were serious
|
5 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs leading to temporary ETR discontinuation
|
8 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs leading to permanent ETR discontinuation
|
8 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs possibly related to ETR
|
23 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs probably related to ETR
|
14 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs very likely related to ETR
|
3 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs at least possibly related to ETR
|
33 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs possibly related to OBR
|
27 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs probably related to OBR
|
12 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs very likely related to OBR
|
5 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs at least possibly related to OBR
|
36 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of at least grade 2 in severity
|
21 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of at least grade 3 in severity
|
3 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: Skin event
|
31 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: severe cutaneous reactions
|
7 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: angioedema
|
4 Patients
|
|
The Number of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: neuropsychiatric events
|
2 Patients
|
PRIMARY outcome
Timeframe: 48 weeksPopulation: The safety analysis was done on the intent-to-treat (ITT) population, which included all patients who received at least one dose of investigational medication.
The percentage of patients with a treatment-emergent adverse event (TEAE) (defined as an event that occurred in the 48-week treatment period during which it emerged \[i.e. started or worsened in severity, relation, or other attribute\], and not in the subsequent study periods, even if the event continued to be present\] are provided below. Adverse events were graded from 1 to 4 in severity using the Division of Acquired Immunodeficiency Syndrome severity scale (grade 1 being less severe and grade 4 being more severe). ETR=etravirine/TMC125; OBR=optimized background regimen
Outcome measures
| Measure |
TMC125
n=101 Participants
TMC125 dosed based on body weight (kg) from 100 mg to 200 mg twice a day
|
|---|---|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
Any TEAE
|
88.1 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs that were fatal
|
0 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs that were serious
|
5.0 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs that were grade 3 or 4 in severity
|
13.9 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs leading to temporary ETR discontinuation
|
7.9 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs at least possibly related to OBR
|
35.6 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of at least grade 2 in severity
|
20.8 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of at least grade 3 in severity
|
3.0 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: Skin event
|
30.7 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: Rash
|
22.8 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: severe cutaneous reactions
|
6.9 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: pancreatic events
|
1.0 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs leading to permanent ETR discontinuation
|
7.9 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs possibly related to ETR
|
22.8 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs probably related to ETR
|
13.9 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs very likely related to ETR
|
3.0 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs at least possibly related to ETR
|
32.7 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs possibly related to OBR
|
26.7 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs probably related to OBR
|
11.9 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs very likely related to OBR
|
5.0 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: angioedema
|
4.0 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: neuropsychiatric events
|
2.0 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: hepatic events
|
0 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: cardiac events
|
0 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: bleeding events
|
0 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: lipid-related events
|
5.9 Percentage of patients
|
|
The Percentage of Patients With Treatment-emergent Adverse Events (TEAEs)
TEAEs of interest: neoplasms
|
1.0 Percentage of patients
|
SECONDARY outcome
Timeframe: Weeks 4-48Population: The intent-to-treat (ITT) population, i.e. all patients who had been enrolled and taken ETR at least once, regardless of their compliance with the protocol was used for this analysis. The table below shows results for "Overall (children and adolescents combined)."
The AUC12h is a Bayesian estimation based on a population pharmacokinetic model and sparse samples collected at each visit over the duration of trial. For each sparse sample taken, the time blood sample was recorded as well as the time of etravirine intake just prior to the time of blood sample.
Outcome measures
| Measure |
TMC125
n=101 Participants
TMC125 dosed based on body weight (kg) from 100 mg to 200 mg twice a day
|
|---|---|
|
Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Area Under the Plasma Concentration-time Curve Over 12 Hours at Steady-state (AUC12h)
|
5216 ng.h/mL
Standard Deviation 4305
|
SECONDARY outcome
Timeframe: Week 48Population: The intent-to-treat (ITT) population, i.e. all patients who had been enrolled and taken ETR at least once, regardless of their compliance with the protocol was used for this analysis. The table below shows results for "Overall (children and adolescents combined)."
Outcome measures
| Measure |
TMC125
n=101 Participants
TMC125 dosed based on body weight (kg) from 100 mg to 200 mg twice a day
|
|---|---|
|
Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Trough Plasma Concentration (C0h)
|
346 ng/mL
Standard Deviation 342
|
SECONDARY outcome
Timeframe: Week 4Population: The intent-to-treat (ITT) population, i.e. all patients who had been enrolled and taken Etravirine/TMC125 (ETR) at least once, regardless of their compliance with the protocol was used for this analysis.
Etravirine/TMC125 (ETR) Cmax was approximated for each individual using the median value of plasma ETR concentrations taken 4 hours postdose (± 1 hour), when available, on the day of the Week 4 visit as shown in the table below.
Outcome measures
| Measure |
TMC125
n=101 Participants
TMC125 dosed based on body weight (kg) from 100 mg to 200 mg twice a day
|
|---|---|
|
Population Pharmacokinetic (PK) Estimates of Etravirine/TMC125 (ETR): Maximum Plasma Concentration (Cmax)
|
589 ng/mL
Standard Deviation 486
|
SECONDARY outcome
Timeframe: Week 24Population: The intent-to-treat (ITT) population, i.e. all patients who had been enrolled and taken Etravirine/TMC125 (ETR) at least once, regardless of their compliance with the protocol was used for this analysis.
Virologic response was defined as the percentage of patients with plasma viral load \< 50 copies/mL at Week 24 calculated according to the non-completer=failure (NC=F) imputation method.
Outcome measures
| Measure |
TMC125
n=101 Participants
TMC125 dosed based on body weight (kg) from 100 mg to 200 mg twice a day
|
|---|---|
|
Percentage of Patients With Virologic Response at Week 24
|
52.5 Percentage of Patients
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: The intent-to-treat (ITT) population, i.e. all patients who had been enrolled and taken Etravirine/TMC125 (ETR) at least once, regardless of their compliance with the protocol was used for this analysis.
Outcome measures
| Measure |
TMC125
n=101 Participants
TMC125 dosed based on body weight (kg) from 100 mg to 200 mg twice a day
|
|---|---|
|
Change From Baseline in Human Immunodeficiency Virus - Type 1 (HIV-1) Ribonucleic Acid (RNA) in Plasma Over Time
|
-1.53 log10 copies/mL
Standard Error 0.132
|
SECONDARY outcome
Timeframe: Baseline, Week 48Population: The intent-to-treat (ITT) population, i.e. all patients who had been enrolled and taken Etravirine/TMC125 (ETR) at least once, regardless of their compliance with the protocol was used for this analysis.
Outcome measures
| Measure |
TMC125
n=101 Participants
TMC125 dosed based on body weight (kg) from 100 mg to 200 mg twice a day
|
|---|---|
|
The Change From Baseline in CD4 Cell Counts Over Time
|
156 10E6 cells/L
Standard Error 22.7
|
SECONDARY outcome
Timeframe: Baseline and Endpoint (up to Week 48)Population: The patients in the intent-to-treat (ITT) population classified as virologic failures were used for this analysis.
Virologic failure (lack of response) was defined as: plasma viral load decline of \< 0.5 log10 from Baseline by Week 8 and/or plasma viral load decline of \<1.0 log10 from Baseline by Week 12. Virologic failure (loss of response) was defined as 2 consecutive measurements of plasma viral load \> 0.5 log10 above the nadir after a minimum of 12 weeks of treatment. The table below provides data for 41 viologic failures of which 30 had mutation data available. In the table below, only the 4 most frequently emerging mutations are presented (emerging in at least 3 patients).
Outcome measures
| Measure |
TMC125
n=41 Participants
TMC125 dosed based on body weight (kg) from 100 mg to 200 mg twice a day
|
|---|---|
|
The Emergence of Non-nucleoside Reverse Transcriptase Inhibitor Resistance-associated Mutations (NNRTI RAMs) in Patients Classified as Virologic Failures
V90I
|
3 Patients
|
|
The Emergence of Non-nucleoside Reverse Transcriptase Inhibitor Resistance-associated Mutations (NNRTI RAMs) in Patients Classified as Virologic Failures
L100I
|
3 Patients
|
|
The Emergence of Non-nucleoside Reverse Transcriptase Inhibitor Resistance-associated Mutations (NNRTI RAMs) in Patients Classified as Virologic Failures
E138A
|
3 Patients
|
|
The Emergence of Non-nucleoside Reverse Transcriptase Inhibitor Resistance-associated Mutations (NNRTI RAMs) in Patients Classified as Virologic Failures
Y181C
|
8 Patients
|
Adverse Events
TMC125
Serious adverse events
| Measure |
TMC125
n=101 participants at risk
TMC125 dosed according to body weight (kg) from 100 mg to 200 mg twice a day
|
|---|---|
|
Eye disorders
Ulcerative keratitis
|
0.99%
1/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
General disorders
Drug resistance
|
0.99%
1/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Injury, poisoning and procedural complications
Drug toxicity
|
0.99%
1/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Injury, poisoning and procedural complications
Overdose
|
0.99%
1/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Investigations
Immunoglobulins
|
0.99%
1/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Investigations
Lymphocyte morphology abnormal
|
0.99%
1/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Investigations
Weight decreased
|
0.99%
1/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Social circumstances
Treatment noncompliance
|
0.99%
1/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
Other adverse events
| Measure |
TMC125
n=101 participants at risk
TMC125 dosed according to body weight (kg) from 100 mg to 200 mg twice a day
|
|---|---|
|
Eye disorders
Conjunctivitis
|
5.9%
6/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Gastrointestinal disorders
Diarrhoea
|
15.8%
16/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Gastrointestinal disorders
Nausea
|
9.9%
10/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Gastrointestinal disorders
Vomiting
|
10.9%
11/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
General disorders
Pyrexia
|
8.9%
9/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Infections and infestations
Bronchitis
|
8.9%
9/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Infections and infestations
Oral herpes
|
5.9%
6/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Infections and infestations
Pharyngitis
|
7.9%
8/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Infections and infestations
Rhinitis
|
5.9%
6/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Infections and infestations
Sinusitis
|
5.9%
6/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Infections and infestations
Upper respiratory tract infection
|
26.7%
27/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Nervous system disorders
Headache
|
8.9%
9/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
12.9%
13/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
5.9%
6/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Skin and subcutaneous tissue disorders
Rash
|
10.9%
11/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
8.9%
9/101
Only subjects who had at least one of the TEAEs listed in the Other (non Serious) AE table are included in the Total no. subjects with Non-Serious Adverse Events.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60