A Study to Evaluate the Pharmacokinetic Profile (How the Body Absorbs, Distributes, Metabolizes and Eliminates a Drug) of TMC125 Plus Tenofovir/Emtricitabine Once Daily With or Without Darunavir/r Once Daily in Antiretroviral (ARV) Naive HIV-1 Patients (Patients Have Never Received ARV Treatment).
Sponsor
Tibotec, Inc (Industry)
Overall Status
Completed
CT.gov ID
NCT00534352
Collaborator
Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA (Industry)
23
1
14
Study Details
Study Description
Brief Summary
The purpose of this study is to determine the pharmacokinetic profile of TMC125 400mg with tenofovir DF/emtricitabine FDC (fixed dose combination) 300/200mg all dosed once daily with and without darunavir/ritonavir 800/100 mg once daily in HIV-1 infected, antiretroviral (ARV) naÃ-ve patients (patients who have never received ARV treatment).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This is a multi-center, open-label (doctors and patients know which drug is being given), Phase IIa clinical trial to evaluate the pharmacokinetic (PK) profile, safety and tolerability of TMC125 dosed once daily with tenofovir/emtricitabine with and without darunavir/ritonavir in antiretroviral naive HIV-1 infected patients. There will be an optional open-label extension phase to evaluate effectiveness, safety and tolerability of continued tenofovir/emtricitabine with darunavir/ritonavir all dosed once daily for 48 weeks. This study will be conducted in the United States at up to 5 sites where 20 patients will initially receive TMC125 400mg with tenofovir DF/emtricitabine FDC 300/200 mg all dosed once daily for 14 days. On Day 15, a blood sample will be obtained and intensive TMC125 pharmacokinetic (PK) values and fasting lipids (check of total cholesterol, direct LDL, HDL, triglycerides) following a 10 hour fast (no eating) will be assessed. Patients will then add darunavir / ritonavir 800/100 mg once a day to the regimen for Days 15 - 29. On Day 29 intensive PK sampling for TMC125, darunavir and ritonavir will be performed and fasting lipids will be evaluated. On Day 29, patients will discontinue TMC125 and continue darunavir/ritonavir 800/100 mg and tenofovir DF/emtricitabine FDC 300/200 mg all dosed once daily. On Day 43, fasting lipids will be assessed. At this point, patients may enter the optional open-label extension phase of the study and continue treatment with darunavir/ritonavir 800mg/100 mg and tenofovir DF/emtricitabine FDC 300/200mg all dosed once daily through 48 total weeks of treatment. The study will consist of a total of 8 visits including 2 intensive PK visits. Within 4 weeks after the Screening Visit, the study site should have received all data to determine a patient's eligibility for the study. The Baseline Visit (Day 1) will be followed by a study visit on Day 8. An intensive PK visit will occur on Day 15. After modification of therapy on Day 15, a study visit will occur on Day 22. A second intensive PK visit will occur on Day 29. On Day 43 a study visit will occur at which point study therapy will be discontinued unless the patient elects to continue in the optional open label extension phase of the study. Patients electing to continue in the open-label extension will have 4 additional study visits at Week 12, 24, 36 and 48. All patients will be asked to return for a 4-week follow-up visit after the completion of study treatment.
During the treatment period, the patient will be seen at regular visits during which the investigator will assess the patient's medical condition, any Adverse Events and study drug compliance. Laboratory evaluations for effectiveness and safety will be done at regular visits as well as blood pressure monitoring. All patients will receive TMC125 400 mg orally (by mouth) once daily. Tenofovir DF 300mg/emtricitabine 200mg will be dosed once daily orally as the fixed dose combination. Darunavir/ritonavir will be dosed 800/100 mg orally once daily. All doses should be administered following a meal.
Study Design
Study Type:
Interventional
Actual Enrollment
:
23 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Multicenter Study to Evaluate the Pharmacokinetic Profile and Safety of TMC125 Plus Tenofovir DF/Emtricitabine All Dosed Once Daily With and Without Darunavir (PREZISTA™)/ Ritonavir Once Daily in Antiretroviral naïve HIV-1 Infected Subjects
Study Start Date
:
Jan 1, 2008
Actual Primary Completion Date
:
May 1, 2008
Actual Study Completion Date
:
Mar 1, 2009
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 001 TMC125; darunavir; ritonavirTMC125 400mg once daily for 4 weeks; Darunavir-800mg once daily for 48 weeks; Ritonavir-100mg once daily for 48 weeks |
Drug: TMC125; darunavir; ritonavir
TMC125 400mg once daily for 4 weeks; Darunavir-800mg once daily for 48 weeks; Ritonavir-100mg once daily for 48 weeks
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Contributing to the Pharmacokinetic (PK) Evaluations: Cmin, Cmax, AUC24 & Css,av [6 weeks]
At visit Days 14 & 28, samples were collected pre-dose and at 1, 2, 3, 4, 6, 9, and 12 hours post-dose. An additional sample was taken at 24 hours (Day 15 or 29 as applicable) post-dose.
Secondary Outcome Measures
- Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia [Day 1 through 42 and Week 48]
Number of Participants with Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia. Worst Grade is based on the National Institute of Allergy and Infectious Diseases Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity grading scale, 0,1,2,3,4 and 5 : None, Mild, Moderate, Severe, Life-threatening and Death.
- Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose- Hypoglycemia [Day 1 through 42 and Week 48]
Number of participants with Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose- Hypoglycemia. Worst Grade is based on the DAIDS toxicity grading scale 0-5: No Toxicity-Death.
- Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin [Day 1 through 42 and Week 48]
Number of participants with Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin. Normal Range: 3.0 - 27.0 ulU/mL
- Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral [Day 1 through 42 and Week 48]
Number of participants with Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral. Worst Grade is based on the DAIDS toxicity grading scale, 0-5 : No Toxicity-Death.
- Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Lipids- High-density Lipoprotein (HDL) [Day 1 through 42 and Week 48]
Number of participants with Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Lipids- High-density lipoprotein (HDL). Normal Range: 40 - 59 mG/dL 1.03 - 1.53 mmol/L
- Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Low-density Lipoprotein (LDL) Direct [Day 1 through 42 and Week 48]
Number of participants with Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Low-density lipoprotein (LDL) Direct. Worst Grade is based on the DAIDS toxicity grading scale, 0-5 : No Toxicity-Death.
- Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Triglycerides [Day 1 through 48 and Week 48]
Number of participants with Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Triglycerides. Worst Grade is based on the DAIDS toxicity grading scale, 0-5 : No Toxicity-Death.
- Virologic Response < 50 HIV-1 RNA Copies/mL (ITT-Observed Case) [Day 8, 14, 22, 28, 42 and Week 48]
Virologic Response < 50 HIV-1 RNA Copies/mL (ITT-Observed Case).
- Log10 Viral Load (HIV-1 RNA Copies/mL): Mean Changes From Baseline(ITT-Observed Case) [Baseline, Day 8, 14, 22, 28 & 42 and Week 48]
Log10 Viral Load (HIV-1 RNA copies/mL): Mean Changes From Baseline(ITT-Observed Case).
- CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline (ITT-Observed Case) [Baseline, Day 8, 14, 22, 28 & 42 ans Week 48]
CD4+ Cell Count (x 10^6 cell/L): Baseline and Median Changes From Baseline (ITT-Observed Case).
- CD4+ Cell Count (Percent): Baseline and Median Changes From Baseline (ITT-Observed Case) [Baseline, Day 8, 14, 22, 28 & 42 and Week 48]
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Documented HIV-1 infection
-
Naive to antiretroviral therapy (never received antiretroviral therapy prior to study)
-
In the opinion of the investigator, have an indication for antiretroviral therapy
-
Able to comply with the protocol requirements
Exclusion Criteria:
-
No previous or current use of antiretroviral medications (ARVs) for the treatment of HIV infection or hepatitis B/C infection with anti-HIV activity
-
No evidence of antiretroviral resistance on current or past resistance assays
-
No chronic hepatitis B and/or C co-infection
-
No grade 3 or 4 laboratory abnormality as defined by National Institute of Allergy and Infectious Diseases Division of Acquired Immunodeficiency Syndrome (DAIDS) grading tables, or a calculated creatinine clearance (CLCr) < 50 mL/min.
-
No known diabetes mellitus or hyperlipidemia requiring lipid-lowering therapy
-
No acute viral hepatitis including, but not limited to A, B, or C.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Tibotec, Inc
- Tibotec Therapeutics, a Division of Ortho Biotech Products, L.P., USA
Investigators
- Study Director: Tibotec, Inc. Clinical Trial, Tibotec, Inc
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00534352
Other Study ID Numbers:
- CR014485
- TMC125HIV2032
First Posted:
Sep 24, 2007
Last Update Posted:
Apr 16, 2015
Last Verified:
Mar 1, 2015
Keywords provided by ,
,
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | The 42-day open-label main treatment phase of this trial was conducted from 10 December 2007 to 27 May 2008. Four investigators from the US participated in this multicenter trial. A total of 35 subjects were screened and of these, 23 subjects entered the trial and started the first treatment phase |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | TDF/FTC +/- TMC125 +/- DRV/Rtv |
|---|---|
| Arm/Group Description | In the first part of the trial (Days 1-14), all subjects received TMC125 400 mg once daily (qd) in combination with fixed dose combinations (FDC) of tenofovir disoproxil (TDF)/emtricitabine (FTC) 300/200 mg qd(Truvada®) for 14 days (Treatment A: TMC125 + TDF/FTC ). On Day 14, 24-hour intensive TMC125 pharmacokinetic sampling took place and fasting lipids were assessed. In the second part of the trial (Days 15-28) darunavir (DRV)/ritonavir (rtv) 800/100 mg qd was added to the regimen (Treatment B: TMC 125 + TDF/FTC + DRV/rtv). On Day 28, 24-hour intensive pharmacokinetic sampling for TMC125, DRV and ritonavir took place and fasting lipids were assessed. In the third part of the trial (Day 29-42), TMC125 was discontinued and subjects received treatment with DRV/rtv 800/100 mg q.d. and TDF/FTC FDC 300/200 mg qd (Treatment C: DRV/rtv + TDF/FTC).On Day 42, fasting lipids were assessed. Subjects discontinued or entered the optional open-label extension period DRV/rtv + TDF/FTC. |
| Period Title: Treatment A: TMC125 + TDF/FTC | |
| STARTED | 23 |
| COMPLETED | 21 |
| NOT COMPLETED | 2 |
| Period Title: Treatment A: TMC125 + TDF/FTC | |
| STARTED | 21 |
| COMPLETED | 21 |
| NOT COMPLETED | 0 |
| Period Title: Treatment A: TMC125 + TDF/FTC | |
| STARTED | 21 |
| COMPLETED | 20 |
| NOT COMPLETED | 1 |
| Period Title: Treatment A: TMC125 + TDF/FTC | |
| STARTED | 18 |
| COMPLETED | 14 |
| NOT COMPLETED | 4 |
Baseline Characteristics
| Arm/Group Title | TDF/FTC +/- TMC125 +/- DRV/Rtv |
|---|---|
| Arm/Group Description | In the first part of the trial (Days 1-14), all subjects received TMC125 400 mg once daily (qd) in combination with fixed dose combinations (FDC) of tenofovir disoproxil (TDF)/emtricitabine (FTC) 300/200 mg qd(Truvada®) for 14 days (Treatment A: TMC125 + TDF/FTC ). On Day 14, 24-hour intensive TMC125 pharmacokinetic sampling took place and fasting lipids were assessed. In the second part of the trial (Days 15-28) darunavir (DRV)/ritonavir (rtv) 800/100 mg qd was added to the regimen (Treatment B: TMC 125 + TDF/FTC + DRV/rtv). On Day 28, 24-hour intensive pharmacokinetic sampling for TMC125, DRV and ritonavir took place and fasting lipids were assessed. In the third part of the trial (Day 29-42), TMC125 was discontinued and subjects received treatment with DRV/rtv 800/100 mg q.d. and TDF/FTC FDC 300/200 mg qd (Treatment C: DRV/rtv + TDF/FTC).On Day 42, fasting lipids were assessed. Subjects discontinued or entered the optional open-label extension period DRV/rtv + TDF/FTC. |
| Overall Participants | 23 |
| Age (Count of Participants) | |
| <=18 years |
0
0%
|
| Between 18 and 65 years |
22
95.7%
|
| >=65 years |
1
4.3%
|
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
35.87
(13.264)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
3
13%
|
| Male |
20
87%
|
| Race/Ethnicity, Customized (participants) [Number] | |
| Black |
9
39.1%
|
| Caucasian / White |
9
39.1%
|
| Hispanic |
5
21.7%
|
| Region of Enrollment (participants) [Number] | |
| United States |
23
100%
|
| CYP2C19 Genotyping (participants) [Number] | |
| CYP2C19*1/CYP2C19*1 : Normal Phenotype |
5
21.7%
|
| CYP2C19*1/CYP2C19*17 : Rapid Phenotype |
5
21.7%
|
| CYP2C19*1/CYP2C19*2 : Intermediate Phenotype |
7
30.4%
|
| CYP2C19*17/CYP2C19*17 : Ultrarapid Phenotype |
1
4.3%
|
| CYP2C19*17/CYP2C19*2 : Normal Phenotype |
2
8.7%
|
| CYP2C19*2/CYP2C19*2 : Poor Phenotype |
1
4.3%
|
| No data |
2
8.7%
|
| CYP2C9 Genotyping (participants) [Number] | |
| CYP2C9*1/CYP2C1*1 : Normal Phenotype |
19
82.6%
|
| CYP2C9*1/CYP2C1*3 : Intermediate Phenotype |
2
8.7%
|
| No data |
2
8.7%
|
| Family History Related to Skin Disease (participants) [Number] | |
| No |
18
78.3%
|
| Yes |
5
21.7%
|
| Body Mass Index (kg/m2) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [kg/m2] |
26.33
(4.629)
|
| Height (cm) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [cm] |
172.73
(8.405)
|
| Weight (kg) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [kg] |
78.58
(13.711)
|
Outcome Measures
| Title | Number of Participants Contributing to the Pharmacokinetic (PK) Evaluations: Cmin, Cmax, AUC24 & Css,av |
|---|---|
| Description | At visit Days 14 & 28, samples were collected pre-dose and at 1, 2, 3, 4, 6, 9, and 12 hours post-dose. An additional sample was taken at 24 hours (Day 15 or 29 as applicable) post-dose. |
| Time Frame | 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intention To Treat (ITT) population |
| Arm/Group Title | Treatment A: TMC125 + TDF/FTC | Treatment B: TMC125 + TDF/FTC + DRV/Rtv |
|---|---|---|
| Arm/Group Description | Treatment A: TMC125 + TDF/FTC. | Treatment B: TMC125 + TDF/FTC + DRV/rtv. |
| Measure Participants | 23 | 21 |
| Number [participants] |
23
100%
|
21
NaN
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Treatment A: TMC125 + TDF/FTC, Treatment B: TMC125 + TDF/FTC + DRV/Rtv |
|---|---|---|
| Comments | Previous studies showed that the intrasubject variability on the log transformed Cmax and AUC12h of TMC125 was less than or equal to 40%. Based on this and with complete data on 20 patients, the 90% CI of the true ratio of the means was expected to be contained within 81-124% of the observed ratio of the means. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Equivalence was shown for Cmin as the 90% confidence intervals (CI) of the LSmean ratio was within the 80-125% limits. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Square (LS) mean ratio |
| Estimated Value | 95.47 | |
| Confidence Interval |
() 90% 82.77 to 110.1 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The results are for the mean ratio of Cmin. Numerator: Treatment B Denominator: Treatment A | |
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Treatment A: TMC125 + TDF/FTC, Treatment B: TMC125 + TDF/FTC + DRV/Rtv |
|---|---|---|
| Comments | Previous studies showed that the intrasubject variability on the log transformed Cmax and AUC12h of TMC125 was less than or equal to 40%. Based on this and with complete data on 20 patients, the 90% CI of the true ratio of the means was expected to be contained within 81-124% of the observed ratio of the means. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Equivalence was shown for Cmax as the 90% confidence intervals (CI) of the LSmean ratio was within the 80-125% limits. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Square (LS) mean ratio |
| Estimated Value | 102.6 | |
| Confidence Interval |
() 90% 92.91 to 113.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The results are for the mean ratio of Cmax. Numerator: Treatment B Denominator: Treatment A | |
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | Treatment A: TMC125 + TDF/FTC, Treatment B: TMC125 + TDF/FTC + DRV/Rtv |
|---|---|---|
| Comments | Previous studies showed that the intrasubject variability on the log transformed Cmax and AUC12h of TMC125 was less than or equal to 40%. Based on this and with complete data on 20 patients, the 90% CI of the true ratio of the means was expected to be contained within 81-124% of the observed ratio of the means. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Equivalence was shown for AUC24 as the 90% confidence intervals (CI) of the LSmean ratio was within the 80-125% limits. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | LS means of ratios |
| Estimated Value | 98.97 | |
| Confidence Interval |
() 90% 89.23 to 109.8 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The results are for the mean ratio of AUC24. Numerator: Treatment B Denominator: Treatment A | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | Treatment A: TMC125 + TDF/FTC, Treatment B: TMC125 + TDF/FTC + DRV/Rtv |
|---|---|---|
| Comments | Previous studies showed that the intrasubject variability on the log transformed Cmax and AUC12h of TMC125 was less than or equal to 40%. Based on this and with complete data on 20 patients, the 90% CI of the true ratio of the means was expected to be contained within 81-124% of the observed ratio of the means. | |
| Type of Statistical Test | Non-Inferiority or Equivalence | |
| Comments | Equivalence was shown for Css,av as the 90% confidence intervals (CI) of the LSmean ratio was within the 80-125% limits. | |
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Least Square (LS) mean ratio |
| Estimated Value | 99.30 | |
| Confidence Interval |
() 90% 89.39 to 110.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | The results are for the mean ratio of Css,av. Numerator: Treatment B Denominator: Treatment A | |
| Title | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia |
|---|---|
| Description | Number of Participants with Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose-Hyperglycemia. Worst Grade is based on the National Institute of Allergy and Infectious Diseases Division of Acquired Immunodeficiency Syndrome (DAIDS) toxicity grading scale, 0,1,2,3,4 and 5 : None, Mild, Moderate, Severe, Life-threatening and Death. |
| Time Frame | Day 1 through 42 and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Treatment A | Treatment B | Treatment C | Optional Extension |
|---|---|---|---|---|
| Arm/Group Description | TMC125 + TDF/FTC | TMC125 + TDF/FTC + DRV/rtv | DRV/rtv + TDF/FTC | DRV/rtv + TDF/FTC |
| Measure Participants | 21 | 21 | 20 | 18 |
| Grade 1 |
1
4.3%
|
2
NaN
|
0
NaN
|
2
NaN
|
| Grade 2 |
1
4.3%
|
0
NaN
|
1
NaN
|
1
NaN
|
| Title | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose- Hypoglycemia |
|---|---|
| Description | Number of participants with Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Glucose- Hypoglycemia. Worst Grade is based on the DAIDS toxicity grading scale 0-5: No Toxicity-Death. |
| Time Frame | Day 1 through 42 and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Treatment A | Treatment B | Treatment C | Optional Extension |
|---|---|---|---|---|
| Arm/Group Description | TMC125 + TDF/FTC | TMC125 + TDF/FTC + DRV/rtv | DRV/rtv + TDF/FTC | DRV/rtv + TDF/FTC |
| Measure Participants | 21 | 21 | 20 | 18 |
| Grade 1 |
0
0%
|
2
NaN
|
0
NaN
|
1
NaN
|
| Grade 2 |
0
0%
|
1
NaN
|
0
NaN
|
0
NaN
|
| Title | Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin |
|---|---|
| Description | Number of participants with Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Glucose- Insulin. Normal Range: 3.0 - 27.0 ulU/mL |
| Time Frame | Day 1 through 42 and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Treatment A | Treatment B | Treatment C | Optional Extension |
|---|---|---|---|---|
| Arm/Group Description | TMC125 + TDF/FTC | TMC125 + TDF/FTC + DRV/rtv | DRV/rtv + TDF/FTC | DRV/rtv + TDF/FTC |
| Measure Participants | 21 | 21 | 19 | 16 |
| Below 3.0 ulU/mL |
1
|
2
|
1
|
1
|
| Above 27.0 ulU/mL |
1
|
3
|
2
|
3
|
| Title | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral |
|---|---|
| Description | Number of participants with Treatment-Emergent Graded Laboratory Abnormalities (Worst Grade): Lipids- Total Cholesteral. Worst Grade is based on the DAIDS toxicity grading scale, 0-5 : No Toxicity-Death. |
| Time Frame | Day 1 through 42 and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Treatment A | Treatment B | Treatment C | Optional Extension |
|---|---|---|---|---|
| Arm/Group Description | TMC125 + TDF/FTC | TMC125 + TDF/FTC + DRV/rtv | DRV/rtv + TDF/FTC | DRV/rtv + TDF/FTC |
| Measure Participants | 21 | 20 | 20 | 7 |
| Grade 1 |
0
0%
|
0
NaN
|
2
NaN
|
1
NaN
|
| Grade 2 |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
| Title | Number of Participants With Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Lipids- High-density Lipoprotein (HDL) |
|---|---|
| Description | Number of participants with Treatment-Emergent Non-Graded Laboratory Abnormalities(Worst Abnormality): Lipids- High-density lipoprotein (HDL). Normal Range: 40 - 59 mG/dL 1.03 - 1.53 mmol/L |
| Time Frame | Day 1 through 42 and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Treatment A | Treatment B | Treatment C | Optional Extension |
|---|---|---|---|---|
| Arm/Group Description | TMC125 + TDF/FTC | TMC125 + TDF/FTC + DRV/rtv | DRV/rtv + TDF/FTC | DRV/rtv + TDF/FTC |
| Measure Participants | 14 | 15 | 15 | 7 |
| Below 40 mG/dL (1.03 mmol/L) |
4
17.4%
|
8
NaN
|
6
NaN
|
2
NaN
|
| Above 59 mG/dL (1.53 mmol/L) |
0
0%
|
0
NaN
|
0
NaN
|
1
NaN
|
| Title | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Low-density Lipoprotein (LDL) Direct |
|---|---|
| Description | Number of participants with Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Low-density lipoprotein (LDL) Direct. Worst Grade is based on the DAIDS toxicity grading scale, 0-5 : No Toxicity-Death. |
| Time Frame | Day 1 through 42 and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Treatment A | Treatment B | Treatment C | Optional Extension |
|---|---|---|---|---|
| Arm/Group Description | TMC125 + TDF/FTC | TMC125 + TDF/FTC + DRV/rtv | DRV/rtv + TDF/FTC | DRV/rtv + TDF/FTC |
| Measure Participants | 21 | 20 | 20 | 7 |
| Grade 1 |
0
0%
|
0
NaN
|
1
NaN
|
1
NaN
|
| Grade 2 |
0
0%
|
0
NaN
|
1
NaN
|
1
NaN
|
| Title | Number of Participants With Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Triglycerides |
|---|---|
| Description | Number of participants with Treatment-Emergent Graded Laboratory Abnormalities(Worst Grade): Lipids- Triglycerides. Worst Grade is based on the DAIDS toxicity grading scale, 0-5 : No Toxicity-Death. |
| Time Frame | Day 1 through 48 and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | Treatment A | Treatment B | Treatment C | Optional Extension |
|---|---|---|---|---|
| Arm/Group Description | TMC125 + TDF/FTC | TMC125 + TDF/FTC + DRV/rtv | DRV/rtv + TDF/FTC | DRV/rtv + TDF/FTC |
| Measure Participants | 20 | 19 | 20 | 7 |
| Grade 1 |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
| Grade 2 |
0
0%
|
0
NaN
|
0
NaN
|
0
NaN
|
| Title | Virologic Response < 50 HIV-1 RNA Copies/mL (ITT-Observed Case) |
|---|---|
| Description | Virologic Response < 50 HIV-1 RNA Copies/mL (ITT-Observed Case). |
| Time Frame | Day 8, 14, 22, 28, 42 and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT |
| Arm/Group Title | TDF/FTC +/- TMC125 +/- DRV/Rtv |
|---|---|
| Arm/Group Description | In the first part of the trial (Days 1-14), all subjects received TMC125 400 mg once daily (qd) in combination with fixed dose combinations (FDC) of tenofovir disoproxil (TDF)/emtricitabine (FTC) 300/200 mg qd(Truvada®) for 14 days (Treatment A: TMC125 + TDF/FTC ). On Day 14, 24-hour intensive TMC125 pharmacokinetic sampling took place and fasting lipids were assessed. In the second part of the trial (Days 15-28) darunavir (DRV)/ritonavir (rtv) 800/100 mg qd was added to the regimen (Treatment B: TMC 125 + TDF/FTC + DRV/rtv). On Day 28, 24-hour intensive pharmacokinetic sampling for TMC125, DRV and ritonavir took place and fasting lipids were assessed. In the third part of the trial (Day 29-42), TMC125 was discontinued and subjects received treatment with DRV/rtv 800/100 mg q.d. and TDF/FTC FDC 300/200 mg qd (Treatment C: DRV/rtv + TDF/FTC).On Day 42, fasting lipids were assessed. Subjects discontinued or entered the optional open-label extension period DRV/rtv + TDF/FTC. |
| Measure Participants | 23 |
| Day 8 (n=19) |
0
0%
|
| Day 14 (n=21) |
3
13%
|
| Day 22 (n=19) |
4
17.4%
|
| Day 28 (n=20) |
6
26.1%
|
| Day 42 (n=20) |
7
30.4%
|
| Week 48 (n=13) |
10
43.5%
|
| Title | Log10 Viral Load (HIV-1 RNA Copies/mL): Mean Changes From Baseline(ITT-Observed Case) |
|---|---|
| Description | Log10 Viral Load (HIV-1 RNA copies/mL): Mean Changes From Baseline(ITT-Observed Case). |
| Time Frame | Baseline, Day 8, 14, 22, 28 & 42 and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT (Observed) |
| Arm/Group Title | TDF/FTC +/- TMC125 +/- DRV/Rtv |
|---|---|
| Arm/Group Description | In the first part of the trial (Days 1-14), all subjects received TMC125 400 mg once daily (qd) in combination with fixed dose combinations (FDC) of tenofovir disoproxil (TDF)/emtricitabine (FTC) 300/200 mg qd(Truvada®) for 14 days (Treatment A: TMC125 + TDF/FTC ). On Day 14, 24-hour intensive TMC125 pharmacokinetic sampling took place and fasting lipids were assessed. In the second part of the trial (Days 15-28) darunavir (DRV)/ritonavir (rtv) 800/100 mg qd was added to the regimen (Treatment B: TMC 125 + TDF/FTC + DRV/rtv). On Day 28, 24-hour intensive pharmacokinetic sampling for TMC125, DRV and ritonavir took place and fasting lipids were assessed. In the third part of the trial (Day 29-42), TMC125 was discontinued and subjects received treatment with DRV/rtv 800/100 mg q.d. and TDF/FTC FDC 300/200 mg qd (Treatment C: DRV/rtv + TDF/FTC).On Day 42, fasting lipids were assessed. Subjects discontinued or entered the optional open-label extension period DRV/rtv + TDF/FTC. |
| Measure Participants | 23 |
| Baseline (n=23) |
4.19
(0.157)
|
| Day 8 (n=19) |
-1.41
(0.094)
|
| Day 14 (n=21) |
-1.71
(0.090)
|
| Day 22 (n=19) |
-1.77
(0.094)
|
| Day 28 (n=20) |
-1.86
(0.123)
|
| Day 42 (n=20) |
-2.04
(0.127)
|
| Week 48 (n=13) |
-2.30
(0.237)
|
| Title | CD4+ Cell Count (x 10^6 Cell/L): Baseline and Median Changes From Baseline (ITT-Observed Case) |
|---|---|
| Description | CD4+ Cell Count (x 10^6 cell/L): Baseline and Median Changes From Baseline (ITT-Observed Case). |
| Time Frame | Baseline, Day 8, 14, 22, 28 & 42 ans Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | TDF/FTC +/- TMC125 +/- DRV/Rtv |
|---|---|
| Arm/Group Description | In the first part of the trial (Days 1-14), all subjects received TMC125 400 mg once daily (qd) in combination with fixed dose combinations (FDC) of tenofovir disoproxil (TDF)/emtricitabine (FTC) 300/200 mg qd(Truvada®) for 14 days (Treatment A: TMC125 + TDF/FTC ). On Day 14, 24-hour intensive TMC125 pharmacokinetic sampling took place and fasting lipids were assessed. In the second part of the trial (Days 15-28) darunavir (DRV)/ritonavir (rtv) 800/100 mg qd was added to the regimen (Treatment B: TMC 125 + TDF/FTC + DRV/rtv). On Day 28, 24-hour intensive pharmacokinetic sampling for TMC125, DRV and ritonavir took place and fasting lipids were assessed. In the third part of the trial (Day 29-42), TMC125 was discontinued and subjects received treatment with DRV/rtv 800/100 mg q.d. and TDF/FTC FDC 300/200 mg qd (Treatment C: DRV/rtv + TDF/FTC).On Day 42, fasting lipids were assessed. Subjects discontinued or entered the optional open-label extension period DRV/rtv + TDF/FTC. |
| Measure Participants | 23 |
| Baseline (n=23) |
403.0
|
| Day 8 (n=20) |
45.5
|
| Day 14 (n=20) |
94.0
|
| Day 22 (n=20) |
59.0
|
| Day 28 (n=21) |
62.0
|
| Day 42 (n=19) |
56.0
|
| Week 48 (n=14) |
160.0
|
| Title | CD4+ Cell Count (Percent): Baseline and Median Changes From Baseline (ITT-Observed Case) |
|---|---|
| Description | |
| Time Frame | Baseline, Day 8, 14, 22, 28 & 42 and Week 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT (Observed) |
| Arm/Group Title | TDF/FTC +/- TMC125 +/- DRV/Rtv |
|---|---|
| Arm/Group Description | In the first part of the trial (Days 1-14), all subjects received TMC125 400 mg once daily (qd) in combination with fixed dose combinations (FDC) of tenofovir disoproxil (TDF)/emtricitabine (FTC) 300/200 mg qd(Truvada®) for 14 days (Treatment A: TMC125 + TDF/FTC ). On Day 14, 24-hour intensive TMC125 pharmacokinetic sampling took place and fasting lipids were assessed. In the second part of the trial (Days 15-28) darunavir (DRV)/ritonavir (rtv) 800/100 mg qd was added to the regimen (Treatment B: TMC 125 + TDF/FTC + DRV/rtv). On Day 28, 24-hour intensive pharmacokinetic sampling for TMC125, DRV and ritonavir took place and fasting lipids were assessed. In the third part of the trial (Day 29-42), TMC125 was discontinued and subjects received treatment with DRV/rtv 800/100 mg q.d. and TDF/FTC FDC 300/200 mg qd (Treatment C: DRV/rtv + TDF/FTC).On Day 42, fasting lipids were assessed. Subjects discontinued or entered the optional open-label extension period DRV/rtv + TDF/FTC. |
| Measure Participants | 23 |
| Baseline (n=23) |
26.2
|
| Day 8 (n=20) |
0.1
|
| Day 14 (n=20) |
4.2
|
| Day 22 (n=20) |
1.8
|
| Day 28 (n=21) |
3.0
|
| Day 42 (n=19) |
4.2
|
| Week 48 (n=14) |
3.8
|
Adverse Events
| Time Frame | Baseline, Day 8, 14, 22, 28, 42 and Week 48 | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||
| Arm/Group Title | Treatment A | Treatment B | Treatment C | Optional Extension | ||||
| Arm/Group Description | TMC125 + TDF/FTC | TMC125 + TDF/FTC + DRV/rtv | DRV/rtv + TDF/FTC | DRV/rtv + TDF/FTC | ||||
All Cause Mortality |
||||||||
| Treatment A | Treatment B | Treatment C | Optional Extension | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Treatment A | Treatment B | Treatment C | Optional Extension | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Burkitt's Lymphoma | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Treatment A | Treatment B | Treatment C | Optional Extension | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/23 (43.5%) | 9/21 (42.9%) | 4/21 (19%) | 13/18 (72.2%) | ||||
| Cardiac disorders | ||||||||
| Sinus Tachycardia | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Eye disorders | ||||||||
| Conjunctival Haemorrhage | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Conjunctivitis | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Gastrointestinal disorders | ||||||||
| Anogenital Dysplasia | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Constipation | 1/23 (4.3%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Diarrhoea | 1/23 (4.3%) | 2/21 (9.5%) | 1/21 (4.8%) | 3/18 (16.7%) | ||||
| Dyspepsia | 0/23 (0%) | 0/21 (0%) | 1/21 (4.8%) | 1/18 (5.6%) | ||||
| Gastrooesophageal Reflux Disease | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Haemorrhoids | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Nausea | 2/23 (8.7%) | 4/21 (19%) | 0/21 (0%) | 2/18 (11.1%) | ||||
| Oral Pain | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Toothache | 0/23 (0%) | 0/21 (0%) | 1/21 (4.8%) | 2/18 (11.1%) | ||||
| General disorders | ||||||||
| Fatigue | 1/23 (4.3%) | 2/21 (9.5%) | 0/21 (0%) | 0/18 (0%) | ||||
| Infections and infestations | ||||||||
| Bronchitis | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Folliculitis | 1/23 (4.3%) | 1/21 (4.8%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Syphilis | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Upper Respiratory Tract Infection | 0/23 (0%) | 1/21 (4.8%) | 1/21 (4.8%) | 1/18 (5.6%) | ||||
| Urinary Tract Infection | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Drug Exposure During Pregnancy | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Investigations | ||||||||
| Blood Urine Present | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Nervous system disorders | ||||||||
| Areflexia | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Dizziness | 1/23 (4.3%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Headache | 2/23 (8.7%) | 1/21 (4.8%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Intracranial Hypotension | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Psychiatric disorders | ||||||||
| Anxiety | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Insomnia | 0/23 (0%) | 1/21 (4.8%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Bronchitis Chronic | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Cough | 1/23 (4.3%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Sinus Congestion | 0/23 (0%) | 1/21 (4.8%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Acne Cystic | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Alopecia | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
| Dermatitus | 0/23 (0%) | 0/21 (0%) | 0/21 (0%) | 2/18 (11.1%) | ||||
| Pruritus | 2/23 (8.7%) | 0/21 (0%) | 0/21 (0%) | 1/18 (5.6%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
If TTCA does not publish within 12 months after study conclusion or after TTCA confirms there will be no multicenter publication, Institution may publish their results from their site individually, provided TTCA has 60 day review for confidentiality and additional 60 day delay for patent application.
Results Point of Contact
| Name/Title | Vice President, Tibotec Therapeutics Clinical Affairs |
|---|---|
| Organization | Tibotec Therapeutics Clinical Affairs, Division of Centocor Ortho Biotech Services, LLC |
| Phone | 877-732-2488 |
Responsible Party:
,
,
ClinicalTrials.gov Identifier:
NCT00534352
Other Study ID Numbers:
- CR014485
- TMC125HIV2032
First Posted:
Sep 24, 2007
Last Update Posted:
Apr 16, 2015
Last Verified:
Mar 1, 2015