TMC114-C211: Trial of an Investigational Protease Inhibitor TMC114 With Ritonavir ("TMC114/r") in HIV-1 Infected Patients Who Have Never Been Treated With Antiretroviral Medications.

Sponsor

Tibotec Pharmaceuticals, Ireland (Industry)

Overall Status

Completed

CT.gov ID

NCT00258557

Collaborator

(none)

692

Enrollment

Locations

Arms

Duration (Months)

7.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy, safety and tolerability of TMC114/r versus Kaletra (a combination pill of lopinavir and ritonavir, ("lpv/rtv") in HIV-1 infected patients who have never been treated with anti-retroviral medications (referred to as "treatment-naïve" patients).

Condition or Disease	Intervention/Treatment	Phase
HIV	Drug: LPV/RTV Drug: TMC-114/RTV	Phase 3

Detailed Description

This is a randomized, controlled, open-label trial to investigate the antiviral activity, tolerability and safety of TMC114/r) versus lpv/rtv in treatment-naive HIV-1 infected patients. Six hundred sixty treatment-naïve HIV-1 infected patients will be randomized in a 1:1 ratio to either 800/100 mg of TMC114/r once daily, or a total daily dose of 800/200 mg of lpv/rtv. All patients will take TMC114/r or lpv/rtv in combination with an NRTI background of Truvada (a combination pill of tenofovir and emtricitabine, "TDF/FTC"). The trial will consist of a screening period of approximately 14 to 28 days and a 96-week treatment period, followed by a 4-week follow-up period. The anti HIV-1 therapy initiated at baseline cannot be changed until the end of the treatment period. After the end of the treatment period (maximum of 96 weeks), patients will be followed for an additional 4 weeks to follow-up on any adverse events or laboratory abnormalities until resolution. Patients who fail either virologically or due to intolerance from the TMC114/r or lpv/rtv therapy, as judged by the investigator, or who meet one of the withdrawal criteria will be withdrawn from the trial and may have the opportunity to participate in the rollover phase of the trial.

The primary efficacy parameter is virologic response defined as a confirmed viral load < 50 copies/mL at Week 48 the objective of this study is to establish non-inferiority of TMC114/r versus lpv/rtv in terms of virologic response at Week 48 using a non-inferiority margin of 12%. To test this hypothesis, a two-sided 95% confidence interval (CI) of the difference in response rate between TMC114/r and lpv/rtv will be derived: If the lower bound of the CI exceeds -12%, non-inferiority will be concluded. Patients will take oral doses for up to 96 weeks of either 800/100mg of TMC114/r 1x/day or 800/200mg of lpv/rtv once daily, each in combination with TDF/FTC. (The 400/100 mg 2x/day dose of lpv/rtv will be used where the 1x/day use of lpv/rtv is not approved).

Study Design

Study Type:

Interventional

Actual Enrollment :

692 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase III Randomized, Controlled, Open-label Trial to Investigate the Antiviral Activity, Tolerability and Safety of TMC114/r in Treatment- Naive HIV-1 Infected Patients.

Study Start Date :

Sep 1, 2005

Actual Primary Completion Date :

Jun 1, 2007

Actual Study Completion Date :

May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 002 TMC-114/RTV two 400 mg tablets of TMC114 + one 100 mg capsule of RTV daily for max. 192 weeks	Drug: TMC-114/RTV two 400 mg tablets of TMC114 + one 100 mg capsule of RTV daily for max. 192 weeks
Active Comparator: 001 LPV/RTV 400/100 mg twice daily or 800/200 mg daily depending on the country for max. 192 weeks	Drug: LPV/RTV 400/100 mg twice daily or 800/200 mg daily depending on the country for max. 192 weeks

Arm

Intervention/Treatment

Experimental: 002

TMC-114/RTV two 400 mg tablets of TMC114 + one 100 mg capsule of RTV daily for max. 192 weeks

Drug: TMC-114/RTV

two 400 mg tablets of TMC114 + one 100 mg capsule of RTV daily for max. 192 weeks

Active Comparator: 001

LPV/RTV 400/100 mg twice daily or 800/200 mg daily depending on the country for max. 192 weeks

Drug: LPV/RTV

400/100 mg twice daily or 800/200 mg daily depending on the country for max. 192 weeks

Outcome Measures

Primary Outcome Measures

Confirmed Virologic Response defined as a Viral Load < 50 copies/mL at Week 48 [48 weeks]

Secondary Outcome Measures

Evaluation of safety, tolerability, and durability of efficacy over 96 weeks of treatment [192 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with documented HIV-1 infection
Screening plasma HIV-1 RNA >= 5000 copies/mL
Patients qualify for treatment initiation based on the investigator's assessments and/or according to treatment guidelines
Patients who can comply with the protocol requirements
General medical condition, in the investigator's opinion, does not interfere with the assessments and the completion of the trial.

Exclusion Criteria:

Presence of any currently active AIDS defining illness or receiving treatment for primary HIV infection
Life expectancy of less than 6 months
Previous or current use of antiretroviral medications (ARVs) for the treatment of HIV-infection or hepatitis B infection with anti-HIV activity
Female -patients who are pregnant or breast-feeding, or are of childbearing potential without use of effective non-hormonal birth control methods or not willing to continue practicing these birth control methods for at least 30 days after the end of the treatment period
-patients with a grade 3 or 4 laboratory abnormality as defined by DAIDS grading, or a calculated creatinine clearance (CLCr) < 70 mL/min

Contacts and Locations

Locations

	City	State	Country
1	Phoenix	Arizona	United States
2	Beverly Hills	California	United States
3	Long Beach	California	United States
4	Los Angeles	California	United States
5	Sacramento	California	United States
6	San Francisco	California	United States
7	Washington	District of Columbia	United States
8	Fort Lauderdale	Florida	United States
9	Jacksonville	Florida	United States
10	Miami Beach	Florida	United States
11	Miami	Florida	United States
12	Orlando	Florida	United States
13	Safety Harbor	Florida	United States
14	Tampa	Florida	United States
15	Vero Beach	Florida	United States
16	Baltimore	Maryland	United States
17	Boston	Massachusetts	United States
18	Las Vegas	Nevada	United States
19	Brooklyn	New York	United States
20	Chapel Hill	North Carolina	United States
21	Winston Salem	North Carolina	United States
22	Philadelphia	Pennsylvania	United States
23	Columbia	South Carolina	United States
24	Houston	Texas	United States
25	Buenos Aires		Argentina
26	Mar Del Plata N/A		Argentina
27	Neuquen		Argentina
28	Brisbane		Australia
29	Darlinghurst		Australia
30	Surry Hills		Australia
31	Westmead N/A		Australia
32	Wien		Austria
33	Brussels		Belgium
34	Gent		Belgium
35	Leuven		Belgium
36	Vancouver	British Columbia	Canada
37	Ottawa	Ontario	Canada
38	Toronto	Ontario	Canada
39	Montreal	Quebec	Canada
40	Providencia		Chile
41	Santiago		Chile
42	Costa Rica		Costa Rica
43	San Jose		Costa Rica
44	Aalborg		Denmark
45	Copenhagen Ø		Denmark
46	Hvidovre		Denmark
47	Bobigny		France
48	Lyon		France
49	Nice		France
50	Orleans Cedex 2		France
51	Paris Cedex 12		France
52	Paris		France
53	Berlin		Germany
54	Erlangen		Germany
55	Freiburg		Germany
56	Hamburg		Germany
57	Köln		Germany
58	Mannheim		Germany
59	Munich		Germany
60	München		Germany
61	Athens		Greece
62	Guatemala		Guatemala
63	Sungai Buloh		Malaysia
64	Ciudad De Mexico		Mexico
65	Del Tlalpan		Mexico
66	Guadalajara N/A		Mexico
67	Mex Ctity		Mexico
68	Panama		Panama
69	San Juan		Puerto Rico
70	Kazan		Russian Federation
71	Krasnodar		Russian Federation
72	Moscow N/A		Russian Federation
73	Saint-Petersburg		Russian Federation
74	Sint Petersburg		Russian Federation
75	Smolensk		Russian Federation
76	St Petersburg		Russian Federation
77	Volgograd		Russian Federation
78	Voronezh		Russian Federation
79	Singapore		Singapore
80	Cape Town		South Africa
81	Dundee		South Africa
82	Johannesburg		South Africa
83	Pretoria		South Africa
84	Barcelona N/A		Spain
85	Barcelona		Spain
86	Zurich N/A		Switzerland
87	Taipei		Taiwan
88	Tiachung		Taiwan
89	Bangkok		Thailand
90	Chiang Mai		Thailand
91	Khon Kaen		Thailand
92	Brighton		United Kingdom
93	London		United Kingdom