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A Study to Determine the Antiviral Activity of TMC310911 When Administered With Ritonavir in Treatment-Naive Human Immunodeficiency Virus - Type 1 (HIV-1) Infected Patients

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ClinicalTrials.gov Identifier: NCT00838162
Recruitment Status : Completed
First Posted : February 6, 2009
Results First Posted : March 7, 2013
Last Update Posted : June 12, 2013
Sponsor:
Information provided by (Responsible Party):
Tibotec Pharmaceuticals, Ireland

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Human Immunodeficiency Virus Type 1
Interventions Drug: TMC310911 75 mg twice daily
Drug: TMC310911 150 mg twice daily
Drug: TMC310911 300 mg twice daily
Drug: TMC310911 300 mg once daily
Drug: Ritonavir 100 mg twice daily
Drug: Ritonavir 100 mg once daily
Enrollment 33
Recruitment Details This study was conducted in Germany.
Pre-assignment Details In total, 41 participants were screened of whom 33 participants were randomized and treated with TMC310911. All treated participants completed the study; there were no dropouts or discontinuations during the study.
Arm/Group Title TMC310911/Rtv 75/100 mg Twice Daily TMC310911/Rtv 150/100 mg Twice Daily TMC310911/Rtv 300/100 mg Twice Daily TMC310911/Rtv 300/100 mg Once a Day
Hide Arm/Group Description TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14 TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14 TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14 TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Period Title: Overall Study
Started 9 8 8 8
Completed 9 8 8 8
Not Completed 0 0 0 0
Arm/Group Title TMC310911/Rtv 75/100 mg Twice Daily TMC310911/Rtv 150/100 mg Twice Daily TMC310911/Rtv 300/100 mg Twice Daily TMC310911/Rtv 300/100 mg Once a Day Total
Hide Arm/Group Description TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14 TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14 TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14 TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14 Total of all reporting groups
Overall Number of Baseline Participants 9 8 8 8 33
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 9 participants 8 participants 8 participants 8 participants 33 participants
29.7  (7.23) 38.1  (8.66) 35.5  (6.87) 37.8  (10.19) 35.1  (8.65)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 9 participants 8 participants 8 participants 8 participants 33 participants
Female
1
  11.1%
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.0%
Male
8
  88.9%
8
 100.0%
8
 100.0%
8
 100.0%
32
  97.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 9 participants 8 participants 8 participants 8 participants 33 participants
White 8 8 8 8 32
Black 1 0 0 0 1
1.Primary Outcome
Title Mean Changes From Baseline in Plasma log10 Human Immunodeficiency Virus Type 1 Ribonucleic Acid (HIV-1 RNA)
Hide Description The antiviral activity of TMC310911 is measured by the change in viral load from baseline in the 14 days of treatment following initiation of treatment with 4 different dosing regimens of TMC310911 coadministered with ritonavir.
Time Frame Baseline (Day 1), Day 8, Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to treat (ITT) population- participants who received at least 1 dose of study medication (TMC310911).
Arm/Group Title TMC310911/Rtv 75/100 mg Twice Daily TMC310911/Rtv 150/100 mg Twice Daily TMC310911/Rtv 300/100 mg Twice Daily TMC310911/Rtv 300/100 mg Once a Day
Hide Arm/Group Description:
TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Overall Number of Participants Analyzed 9 8 8 8
Mean (Standard Error)
Unit of Measure: log10 copies/mL
Baseline 4.72  (0.245) 4.36  (0.259) 4.78  (0.161) 4.71  (0.116)
Day 8 -1.30  (0.126) -1.14  (0.147) -1.07  (0.104) -1.06  (0.144)
Day 15 -1.53  (0.117) -1.79  (0.192) -1.69  (0.103) -1.55  (0.160)
2.Secondary Outcome
Title Number of Participants With Virologic Response at Any Timepoint During the 14-day Treatment Period
Hide Description Virologic response is a viral load test result below a chosen threshold value (less than 50 copies/mL, less than 400 copies/mL, or at least 1 log drop in viral load) at any timepoint during a 14-day treatment of 4 different dose regimens of TMC310911 coadministered with 100 mg ritonavir.
Time Frame 14 days
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) Population- all randomized participants who received at least 1 dose of study medication (TMC310911)
Arm/Group Title TMC310911/Rtv 75/100 mg Twice Daily TMC310911/Rtv 150/100 mg Twice Daily TMC310911/Rtv 300/100 mg Twice Daily TMC310911/Rtv 300/100 mg Once a Day
Hide Arm/Group Description:
TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Overall Number of Participants Analyzed 9 8 8 8
Measure Type: Number
Unit of Measure: Participants
Viral load less than 50 copies/mL 0 1 0 0
Viral load less than 400 copies/mL 3 4 1 0
At least 1 log10 Viral Load Drop 9 8 8 7
3.Secondary Outcome
Title Mean Changes From Baseline in CD4+ Cell Count
Hide Description [Not Specified]
Time Frame Baseline (Day 1), Day 8, Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) Population - all randomized participants who received at least 1 dose of study medication (TMC310911)
Arm/Group Title TMC310911/Rtv 75/100 mg Twice Daily TMC310911/Rtv 150/100 mg Twice Daily TMC310911/Rtv 300/100 mg Twice Daily TMC310911/Rtv 300/100 mg Once a Day
Hide Arm/Group Description:
TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Overall Number of Participants Analyzed 9 8 8 8
Mean (Standard Error)
Unit of Measure: x 1000000 cells/L
Baseline 575.7  (56.97) 464.9  (61.32) 494.0  (70.43) 479.6  (39.16)
Day 8 -21.0  (41.23) 40.3  (45.19) -14.8  (47.59) 17.9  (48.20)
Day 15 -33.7  (27.04) -2.8  (31.44) -2.0  (41.23) 92.5  (58.70)
4.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) of TMC310911
Hide Description [Not Specified]
Time Frame Day 1 and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC310911)
Arm/Group Title TMC310911/Rtv 75/100 mg Twice Daily TMC310911/Rtv 150/100 mg Twice Daily TMC310911/Rtv 300/100 mg Twice Daily TMC310911/Rtv 300/100 mg Once a Day
Hide Arm/Group Description:
TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Overall Number of Participants Analyzed 9 8 8 8
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 1 487.9  (450.3) 623.0  (358.1) 706.3  (553.2) 1924  (1048)
Day 14 589.7  (554.1) 1674  (652.3) 2256  (961.9) 2963  (1920)
5.Secondary Outcome
Title Time to Reach the Maximum Plasma Concentration (Tmax) of TMC310911
Hide Description [Not Specified]
Time Frame Day 1 and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC310911)
Arm/Group Title TMC310911/Rtv 75/100 mg Twice Daily TMC310911/Rtv 150/100 mg Twice Daily TMC310911/Rtv 300/100 mg Twice Daily TMC310911/Rtv 300/100 mg Once a Day
Hide Arm/Group Description:
TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Overall Number of Participants Analyzed 9 8 8 8
Median (Full Range)
Unit of Measure: hours
Day 1
5.02
(2.00 to 12.00)
5.00
(3.00 to 8.12)
5.06
(5.00 to 12.17)
5.00
(2.00 to 5.02)
Day 14
4.98
(1.00 to 8.00)
3.00
(1.00 to 5.03)
3.87
(0.00 to 5.02)
3.02
(1.02 to 5.03)
6.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve (AUC12) From the Time of Administration of TMC310911 up to 12 Hours After Dosing
Hide Description [Not Specified]
Time Frame Day 1 and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC310911)
Arm/Group Title TMC310911/Rtv 75/100 mg Twice Daily TMC310911/Rtv 150/100 mg Twice Daily TMC310911/Rtv 300/100 mg Twice Daily TMC310911/Rtv 300/100 mg Once a Day
Hide Arm/Group Description:
TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Overall Number of Participants Analyzed 8 8 7 7
Mean (Standard Deviation)
Unit of Measure: ng.h/mL
Day 1 2519  (2123) 2735  (1572) 2990  (2245) 10040  (6122)
Day 14 4031  (3845) 10680  (3147) 16010  (8229) 17520  (11610)
7.Secondary Outcome
Title Predose Plasma Concentration (C0h) of TMC310911
Hide Description [Not Specified]
Time Frame Day 2, Day 3, Day 4, Day 6, Day 8, Day 10, Day 12 and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC310911).
Arm/Group Title TMC310911/Rtv 75/100 mg Twice Daily TMC310911/Rtv 150/100 mg Twice Daily TMC310911/Rtv 300/100 mg Twice Daily TMC310911/Rtv 300/100 mg Once a Day
Hide Arm/Group Description:
TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Overall Number of Participants Analyzed 9 8 8 8
Mean (Standard Deviation)
Unit of Measure: ng/mL
Day 2 79.95  (104.1) 207.7  (122.9) 231.9  (199.9) 45.48  (28.94)
Day 3 93.98  (92.90) 448.0  (266.1) 586.3  (454.2) 125.9  (69.01)
Day 4 88.94  (113.6) 291.3  (170.2) 1035  (552.2) 191.0  (175.7)
Day 6 119.1  (182.1) 443.0  (284.7) 960.5  (506.9) 250.0  (236.1)
Day 8 134.5  (179.0) 665.9  (461.1) 1028  (724.1) 239.6  (242.6)
Day 10 78.51  (57.88) 394.4  (134.4) 736.1  (435.0) 251.7  (211.0)
Day 12 104.6  (82.91) 518.6  (288.7) 1110  (547.5) 250.2  (181.9)
Day 14 152.5  (248.2) 420.9  (244.6) 924.8  (527.9) 209.9  (187.2)
8.Secondary Outcome
Title Average Steady-state Plasma Concentration (Css,av) of TMC310911
Hide Description [Not Specified]
Time Frame Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC310911).
Arm/Group Title TMC310911/Rtv 75/100 mg Twice Daily TMC310911/Rtv 150/100 mg Twice Daily TMC310911/Rtv 300/100 mg Twice Daily TMC310911/Rtv 300/100 mg Once a Day
Hide Arm/Group Description:
TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Overall Number of Participants Analyzed 8 7 7 8
Mean (Standard Deviation)
Unit of Measure: ng/mL
336.2  (321.3) 889.6  (262.6) 1340  (689.6) 887.3  (567.5)
9.Secondary Outcome
Title Fluctuation Index of TMC310911
Hide Description Fluctuation index, ie, percentage fluctuation: variation between maximum (Cmax) and minimum (Cmin) plasma concentration at steady-state, calculated as: 100 x ([Cmax-Cmin]/Css,av). Css,av is an average steady-state plasma concentration.
Time Frame Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat (ITT) population - all randomized participants who received at least 1 dose of study medication (TMC310911)
Arm/Group Title TMC310911/Rtv 75/100 mg Twice Daily TMC310911/Rtv 150/100 mg Twice Daily TMC310911/Rtv 300/100 mg Twice Daily TMC310911/Rtv 300/100 mg Once a Day
Hide Arm/Group Description:
TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14
TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
Overall Number of Participants Analyzed 8 7 7 8
Mean (Standard Deviation)
Unit of Measure: Percent ng/mL
181.0  (80.00) 161.3  (29.22) 129.2  (52.89) 331.8  (55.47)
Time Frame Up to 4 weeks after the last dose administration of study medication
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title TMC310911/Rtv 75/100 mg Twice Daily TMC310911/Rtv 150/100 mg Twice Daily TMC310911/Rtv 300/100 mg Twice Daily TMC310911/Rtv 300/100 mg Once a Day
Hide Arm/Group Description TMC310911 75 mg + ritonavir 100 mg twice daily on Days 1 to 14 TMC310911 150 mg + ritonavir 100 mg twice daily on Days 1 to 14 TMC310911 300 mg + ritonavir 100 mg twice daily on Days 1 to 14 TMC310911 300 mg + ritonavir 100 mg once a day on Days 1 to 14
All-Cause Mortality
TMC310911/Rtv 75/100 mg Twice Daily TMC310911/Rtv 150/100 mg Twice Daily TMC310911/Rtv 300/100 mg Twice Daily TMC310911/Rtv 300/100 mg Once a Day
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
TMC310911/Rtv 75/100 mg Twice Daily TMC310911/Rtv 150/100 mg Twice Daily TMC310911/Rtv 300/100 mg Twice Daily TMC310911/Rtv 300/100 mg Once a Day
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/9 (0.00%)   0/8 (0.00%)   0/8 (0.00%)   0/8 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
TMC310911/Rtv 75/100 mg Twice Daily TMC310911/Rtv 150/100 mg Twice Daily TMC310911/Rtv 300/100 mg Twice Daily TMC310911/Rtv 300/100 mg Once a Day
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/9 (55.56%)   5/8 (62.50%)   6/8 (75.00%)   3/8 (37.50%) 
Eye disorders         
Conjunctivitis * 1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Gastrointestinal disorders         
Abdominal pain upper * 1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Abnormal faeces * 1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Diarrhoea * 1  1/9 (11.11%)  1/8 (12.50%)  1/8 (12.50%)  0/8 (0.00%) 
Dry mouth * 1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Eructation * 1  0/9 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Flatulence * 1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Frequent bowel movements * 1  0/9 (0.00%)  1/8 (12.50%)  1/8 (12.50%)  0/8 (0.00%) 
Nausea * 1  1/9 (11.11%)  3/8 (37.50%)  0/8 (0.00%)  0/8 (0.00%) 
Toothache * 1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Vomiting * 1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/8 (0.00%) 
General disorders         
Discomfort * 1  0/9 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Fatigue * 1  3/9 (33.33%)  2/8 (25.00%)  4/8 (50.00%)  0/8 (0.00%) 
Influenza like illness * 1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Infections and infestations         
Cytomegalovirus hepatitis * 1  0/9 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Folliculitis * 1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/8 (0.00%) 
Genital herpes * 1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Nasopharyngitis * 1  1/9 (11.11%)  0/8 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Respiratory tract infection * 1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/8 (0.00%) 
Injury, poisoning and procedural complications         
Skeletal injury * 1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Investigations         
Alanine aminotransferase increased * 1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/8 (0.00%) 
Aspartate aminotransferase increased * 1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/8 (0.00%) 
Musculoskeletal and connective tissue disorders         
Muscle spasms * 1  0/9 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Nervous system disorders         
Dizziness * 1  0/9 (0.00%)  0/8 (0.00%)  1/8 (12.50%)  0/8 (0.00%) 
Headache * 1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  1/8 (12.50%) 
Renal and urinary disorders         
Micturition urgency * 1  2/9 (22.22%)  0/8 (0.00%)  0/8 (0.00%)  0/8 (0.00%) 
Skin and subcutaneous tissue disorders         
Night sweats * 1  0/9 (0.00%)  0/8 (0.00%)  0/8 (0.00%)  1/8 (12.50%) 
Skin discolouration * 1  0/9 (0.00%)  1/8 (12.50%)  0/8 (0.00%)  0/8 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: VP Head of Discovery & Early Development
Organization: Jan-Cil UK
Phone: 44 1494 553458
Responsible Party: Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier: NCT00838162     History of Changes
Other Study ID Numbers: CR015952
TMC310911-TIDP21-C201 ( Other Identifier: Tibotec Pharmaceuticals, Ireland )
2008-008190-58 ( EudraCT Number )
First Submitted: February 5, 2009
First Posted: February 6, 2009
Results First Submitted: January 30, 2013
Results First Posted: March 7, 2013
Last Update Posted: June 12, 2013