VERxVE Study on Efficacy and Safety of Nevirapine XR in Comparison to Nevirapine IR With Truvada in Naive HIV+ Patients

• Sponsor: Boehringer Ingelheim (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00561925
• Collaborator: (none)
• Enrollment: 1,068
• Locations: 202
• Arms: 2
• Patients Per Site: 5.3

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the efficacy of 400 mg QD nevirapine extended release (NVP XR) formulation versus 200 mg BID nevirapine immediate release (NVP IR) in ARV therapy naïve HIV-1 infected patients after 48 weeks of treatment. Secondary objectives are to evaluate safety and pharmacokinetics of NVP XR and NVP IR.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: nevirapine IR; Drug: nevirapine XR	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1068 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double
• Primary Purpose: Treatment
• Official Title: A Randomised, Double Blind, Double Dummy, Parallel Group, Active Controlled Trial to Evaluate the Antiviral Efficacy of 400 mg QD neVirapine Extended Release Formulation in Comparison to 200 mg BID neVirapinE Immediate Release in Combination With Truvada® in Antiretroviral Therapy naïve HIV-1 Infected Patients (VERxVE)
• Study Start Date: Nov 1, 2007
• Actual Primary Completion Date: Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: nevirapine XR 400 mg QD	Drug: nevirapine XR; 400 mg QD
Active Comparator: nevirapine IR 200 mg BID	Drug: nevirapine IR; 200 mg BID

Outcome Measures

Primary Outcome Measures

1. Comparison of Proportion of Virologic Response at Week 48 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population [week 48]

   Primary endpoint was the number of patients with a sustained virologic response through week 48 using LLOQ = 50 copies/mL

Secondary Outcome Measures

1. Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population [week 0 to 144]

2. Proportion of Sustained Virologic Response at Week 144 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population [week 144]

   Endpoint was the number of patients with a sustained virologic response through week 144 using LLOQ = 50 copies/mL

3. Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population [week 0 to 144]

4. Comparison of HIV-1 Viral Load (log10 Copies/mL) Change From Baseline at Week 144, Full Analysis Set Population [baseline, week 144]

5. Comparison of CD4+ Cell Count (Cells/Cubic Millimeter) Change From Baseline at Week 144, Full Analysis Set Population [baseline, week 144]

6. Occurrence of Rashes [until last patient completed 144 weeks (up to 193 weeks)]

   Frequency of patients with drug related rash events by functional grouping

7. Occurrence of Elevations in Laboratory Measurement by DAIDS Grade [until last patient completed 144 weeks (up to 193 weeks)]

8. Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication [week 0 to 144]

9. Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities [week 0 to 72]

10. Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities [week 0 to 72]

11. Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events [week 0 to 72]

12. Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash [week 0 to 72]

13. Relative Bioavailability Trough C_pre,ss,1 [week 132]

    Relative bioavailability measured of trough concentrations. Analysis based on adjusted by-treatment geometric means, the adjusted geometric mean ratio of NVP XR : NVP IR and it's 90% confidence interval with p-value and the inter-individual geometric coefficient of variation.

14. Occurrence of Hepatic Events [until last patient completed 144 weeks (up to 193 weeks)]

    Frequency of patients with hepatitis symptoms

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

1. Signed informed consent in accordance with Good Clinical Practice and local regulatory requirements prior to trial participation

2. HIV-1 infected males or females >= 18 years of age with positive serology (ELISA) confirmed by Western blot

3. No previous antiretroviral treatment

4. Males with CD4+ counts >50 - <400 cells/ml or females with CD4+ counts >50-<250 cells/ml

5. Adequate renal function defined as a calculated creatinine clearance (CLCr) greater than or equal to 50 mL/min according to the Cockcroft-Gault formula as follows:

Male: (140 - age in years) x (weight in kg) divided by 72 x (serum creatinine in mg/dl) = CLCr (mL/min).

Female: (140 - age in years) x (weight in kg) divided by 72 x (serum creatinine in mg/dl) x 0.85 = CLCr (mL/min).

1. Karnofsky score >70 (see Appendix 10.4)

2. An HIV-1 viral load of 1,000 copies/mL

3. Willingness to initiate CD4+ cell count-guided chemoprophylaxis to prevent important opportunistic infections as defined in Appendix 10.2

4. Willingness to abstain from ingesting substances which may alter plasma study drug levels by interaction with the cytochrome P450 system (listed in Appendix 10.3) during the study.

5. For centers participating in the PK substudy only: Written informed consent in accordance with GCP and local legislation for participation in the PK substudy. Refusal to participate in the PK substudy is not an exclusion criterion for participation in the trial. Only study centers with previous experience and equipped in handling PK samples are eligible for participation in the substudy.

Exclusion criteria:

1. Active drug abuse or chronic alcoholism at the investigator's discretion

2. Active hepatitis B or C disease, defined as HBsAg-positive and HBV-DNA-positive or HCV-RNA-positive

3. Female patients of child-bearing potential who: are pregnant at screening; are breast feeding; are planning to become pregnant; are not willing to use a barrier method of contraception, or; are not willing to use methods of contraception other than ethinyl estradiol containing oral contraceptives Note: During participation in this study, females and males have to use barrier methods of contraception in addition or instead of ethinyl estradiol containing oral contraceptives.

4. Laboratory parameters >DAIDS Grade 2

5. ALT/AST > DAIDS Grade 1

6. Hypersensitivity to any ingredients of the test products

7. Previous use of Viramune® (nevirapine) or any other antiretroviral agents (does not include use of single dose NVP for the prevention of mother to child transmission)

8. Resistance to NNRTIs or either one of the components of Truvada® (emtricitabine or tenofovir disoproxil fumarate) or lamivudine (3TC) based on HIV-1 genotypic resistance testing report obtained at screening

9. Patients who are receiving other concomitant treatments which are not permitted, as described in the prescribing information

10. Use of investigational medications (any experimental agent other than the study regimen) within 30 days before study entry or during the trial

11. Use of immunomodulatory drugs within 30 days before study entry or during the trial (e.g., interferon, cyclosporin, hydroxyurea, interleukin 2)

12. Patients who have been diagnosed with malignant disease

13. Patients who in the opinion of the investigator are not candidates for inclusion in the study

14. Patient with Progressive Multifocal Leukoencephalopathy (PML), Visceral Kaposi's Sarcoma (KS), and/or any lymphoma

15. Any AIDS defining illness that is unresolved, symptomatic or not stable on treatment for at least 12 weeks at screening visit

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	1100.1486.0040 Boehringer Ingelheim Investigational Site	Birmingham	Alabama	United States
2	1100.1486.0013 Boehringer Ingelheim Investigational Site	Phoenix	Arizona	United States
3	1100.1486.0017 Boehringer Ingelheim Investigational Site	Bakersfield	California	United States
4	1100.1486.0001 Boehringer Ingelheim Investigational Site	Beverly Hills	California	United States
5	1100.1486.0057 Boehringer Ingelheim Investigational Site	Beverly Hills	California	United States
6	1100.1486.0059 Boehringer Ingelheim Investigational Site	Beverly Hills	California	United States
7	1100.1486.0035 Boehringer Ingelheim Investigational Site	Long Beach	California	United States
8	1100.1486.0025 Boehringer Ingelheim Investigational Site	Los Angeles	California	United States
9	1100.1486.0034 Boehringer Ingelheim Investigational Site	Los Angeles	California	United States
10	1100.1486.0041 Boehringer Ingelheim Investigational Site	Los Angeles	California	United States
11	1100.1486.0032 Boehringer Ingelheim Investigational Site	Sacramento	California	United States
12	1100.1486.0028 Boehringer Ingelheim Investigational Site	San Diego	California	United States
13	1100.1486.0023 Boehringer Ingelheim Investigational Site	Washington	District of Columbia	United States
14	1100.1486.0029 Boehringer Ingelheim Investigational Site	Washington	District of Columbia	United States
15	1100.1486.0048 Boehringer Ingelheim Investigational Site	Washington	District of Columbia	United States
16	1100.1486.0037 Boehringer Ingelheim Investigational Site	Clearwater	Florida	United States
17	1100.1486.0043 Boehringer Ingelheim Investigational Site	Fort Lauderdale	Florida	United States
18	1100.1486.0007 Boehringer Ingelheim Investigational Site	Miami Beach	Florida	United States
19	1100.1486.0012 Boehringer Ingelheim Investigational Site	Miami	Florida	United States
20	1100.1486.0039 Boehringer Ingelheim Investigational Site	Orlando	Florida	United States
21	1100.1486.0050 Boehringer Ingelheim Investigational Site	Vero Beach	Florida	United States
22	1100.1486.0014 Boehringer Ingelheim Investigational Site	Wilton Manors	Florida	United States
23	1100.1486.0031 Boehringer Ingelheim Investigational Site	Atlanta	Georgia	United States
24	1100.1486.0010 Boehringer Ingelheim Investigational Site	Macon	Georgia	United States
25	1100.1486.0053 Boehringer Ingelheim Investigational Site	Boise	Idaho	United States
26	1100.1486.0002 Boehringer Ingelheim Investigational Site	Chicago	Illinois	United States
27	1100.1486.0026 Boehringer Ingelheim Investigational Site	Chicago	Illinois	United States
28	1100.1486.0020 Boehringer Ingelheim Investigational Site	Lexington	Kentucky	United States
29	1100.1486.0019 Boehringer Ingelheim Investigational Site	Berkley	Michigan	United States
30	1100.1486.0006 Boehringer Ingelheim Investigational Site	Kansas City	Missouri	United States
31	1100.1486.0027 Boehringer Ingelheim Investigational Site	St. Louis	Missouri	United States
32	1100.1486.0055 Boehringer Ingelheim Investigational Site	Charlotte	North Carolina	United States
33	1100.1486.0003 Boehringer Ingelheim Investigational Site	Huntersville	North Carolina	United States
34	1100.1486.0005 Boehringer Ingelheim Investigational Site	Akron	Ohio	United States
35	1100.1486.0004 Boehringer Ingelheim Investigational Site	Austin	Texas	United States
36	1100.1486.0018 Boehringer Ingelheim Investigational Site	Dallas	Texas	United States
37	1100.1486.0038 Boehringer Ingelheim Investigational Site	Dallas	Texas	United States
38	1100.1486.0044 Boehringer Ingelheim Investigational Site	Fort Worth	Texas	United States
39	1100.1486.0054 Boehringer Ingelheim Investigational Site	Harlingen	Texas	United States
40	1100.1486.0009 Boehringer Ingelheim Investigational Site	Houston	Texas	United States
41	1100.1486.0046 Boehringer Ingelheim Investigational Site	Annandale	Virginia	United States
42	1100.1486.5401 Boehringer Ingelheim Investigational Site	Capital Federal		Argentina
43	1100.1486.5402 Boehringer Ingelheim Investigational Site	Capital Federal		Argentina
44	1100.1486.5404 Boehringer Ingelheim Investigational Site	Capital Federal		Argentina
45	1100.1486.5407 Boehringer Ingelheim Investigational Site	Capital Federal		Argentina
46	1100.1486.5408 Boehringer Ingelheim Investigational Site	Capital Federal		Argentina
47	1100.1486.5403 Boehringer Ingelheim Investigational Site	Mar del Plata		Argentina
48	1100.1486.5409 Boehringer Ingelheim Investigational Site	Quilmes		Argentina
49	1100.1486.5405 Boehringer Ingelheim Investigational Site	Rosario		Argentina
50	1100.1486.6101 Boehringer Ingelheim Investigational Site	Darlinghurst	New South Wales	Australia
51	1100.1486.6102 Boehringer Ingelheim Investigational Site	Darlinghurst	New South Wales	Australia
52	1100.1486.6104 Boehringer Ingelheim Investigational Site	Surry Hills	New South Wales	Australia
53	1100.1486.6103 Boehringer Ingelheim Investigational Site	Brisbane	Queensland	Australia
54	1100.1486.3208 Boehringer Ingelheim Investigational Site	Brugge		Belgium
55	1100.1486.3207 Boehringer Ingelheim Investigational Site	Brussel		Belgium
56	1100.1486.3201 Boehringer Ingelheim Investigational Site	Bruxelles		Belgium
57	1100.1486.3203 Boehringer Ingelheim Investigational Site	Bruxelles		Belgium
58	1100.1486.3205 Boehringer Ingelheim Investigational Site	Bruxelles		Belgium
59	1100.1486.3209 Boehringer Ingelheim Investigational Site	Charleroi		Belgium
60	1100.1486.3202 Boehringer Ingelheim Investigational Site	Gent		Belgium
61	1100.1486.3204 Boehringer Ingelheim Investigational Site	Liège		Belgium
62	1100.1486.3206 Boehringer Ingelheim Investigational Site	Liège		Belgium
63	1100.1486.2605 Boehringer Ingelheim Investigational Site	Francistown		Botswana
64	1100.1486.2601 Boehringer Ingelheim Investigational Site	Gaborone		Botswana
65	1100.1486.2603 Boehringer Ingelheim Investigational Site	Gaborone		Botswana
66	1100.1486.1002 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia	Canada
67	1100.1486.1004 Boehringer Ingelheim Investigational Site	Winnipeg	Manitoba	Canada
68	1100.1486.1013 Boehringer Ingelheim Investigational Site	Toronto	Ontario	Canada
69	1100.1486.1016 Boehringer Ingelheim Investigational Site	Toronto	Ontario	Canada
70	1100.1486.1005 Boehringer Ingelheim Investigational Site	Montreal	Quebec	Canada
71	1100.1486.1010 Boehringer Ingelheim Investigational Site	Montreal	Quebec	Canada
72	1100.1486.1014 Boehringer Ingelheim Investigational Site	Montreal	Quebec	Canada
73	1100.1486.1011 Boehringer Ingelheim Investigational Site	Quebec (Ste Foy)	Quebec	Canada
74	1100.1486.3305A Boehringer Ingelheim Investigational Site	Angers		France
75	1100.1486.3305B Boehringer Ingelheim Investigational Site	Angers		France
76	1100.1486.3307A Boehringer Ingelheim Investigational Site	Bondy		France
77	1100.1486.3317A Boehringer Ingelheim Investigational Site	Bordeaux Cedex		France
78	1100.1486.3316A Boehringer Ingelheim Investigational Site	Brest Cedex		France
79	1100.1486.3316B Boehringer Ingelheim Investigational Site	Brest Cedex		France
80	1100.1486.3314E Boehringer Ingelheim Investigational Site	Caen cedex 5		France
81	1100.1486.3304A Boehringer Ingelheim Investigational Site	Clamart		France
82	1100.1486.3308A Boehringer Ingelheim Investigational Site	Lyon Cedex 3		France
83	1100.1486.3308C Boehringer Ingelheim Investigational Site	Lyon Cedex 3		France
84	1100.1486.3301A Boehringer Ingelheim Investigational Site	Nantes		France
85	1100.1486.3301B Boehringer Ingelheim Investigational Site	Nantes		France
86	1100.1486.3301C Boehringer Ingelheim Investigational Site	Nantes		France
87	1100.1486.3301D Boehringer Ingelheim Investigational Site	Nantes		France
88	1100.1486.3301E Boehringer Ingelheim Investigational Site	Nantes		France
89	1100.1486.3301F Boehringer Ingelheim Investigational Site	Nantes		France
90	1100.1486.3301G Boehringer Ingelheim Investigational Site	Nantes		France
91	1100.1486.3301H Boehringer Ingelheim Investigational Site	Nantes		France
92	1100.1486.3301I Boehringer Ingelheim Investigational Site	Nantes		France
93	1100.1486.3306A Boehringer Ingelheim Investigational Site	Nice cedex 3		France
94	1100.1486.3303A Boehringer Ingelheim Investigational Site	Paris		France
95	1100.1486.3303B Boehringer Ingelheim Investigational Site	Paris		France
96	1100.1486.3303C Boehringer Ingelheim Investigational Site	Paris		France
97	1100.1486.3303D Boehringer Ingelheim Investigational Site	Paris		France
98	1100.1486.3312A Boehringer Ingelheim Investigational Site	Paris		France
99	1100.1486.3312B Boehringer Ingelheim Investigational Site	Paris		France
100	1100.1486.3309A Boehringer Ingelheim Investigational Site	Saint Etienne		France
101	1100.1486.3309B Boehringer Ingelheim Investigational Site	Saint Etienne		France
102	1100.1486.3318A Boehringer Ingelheim Investigational Site	Toulon cedex		France
103	1100.1486.3318B Boehringer Ingelheim Investigational Site	Toulon cedex		France
104	1100.1486.3318C Boehringer Ingelheim Investigational Site	Toulon cedex		France
105	1100.1486.3318D Boehringer Ingelheim Investigational Site	Toulon cedex		France
106	1100.1486.3302A Boehringer Ingelheim Investigational Site	Toulouse cedex 9		France
107	1100.1486.3302B Boehringer Ingelheim Investigational Site	Toulouse cedex 9		France
108	1100.1486.3302C Boehringer Ingelheim Investigational Site	Toulouse cedex 9		France
109	1100.1486.3310A Boehringer Ingelheim Investigational Site	Villeneuve St Georges cedex		France
110	1100.1486.4902 Boehringer Ingelheim Investigational Site	Berlin		Germany
111	1100.1486.4928 Boehringer Ingelheim Investigational Site	Berlin		Germany
112	1100.1486.4932 Boehringer Ingelheim Investigational Site	Bochum		Germany
113	1100.1486.4922 Boehringer Ingelheim Investigational Site	Bonn		Germany
114	1100.1486.4911 Boehringer Ingelheim Investigational Site	Dortmund		Germany
115	1100.1486.4919 Boehringer Ingelheim Investigational Site	Düsseldorf		Germany
116	1100.1486.4908 Boehringer Ingelheim Investigational Site	Erlangen		Germany
117	1100.1486.4906 Boehringer Ingelheim Investigational Site	Essen		Germany
118	1100.1486.4916 Boehringer Ingelheim Investigational Site	Frankfurt/Main		Germany
119	1100.1486.4929 Boehringer Ingelheim Investigational Site	Frankfurt/Main		Germany
120	1100.1486.4926 Boehringer Ingelheim Investigational Site	Frankfurt		Germany
121	1100.1486.4901 Boehringer Ingelheim Investigational Site	Freiburg		Germany
122	1100.1486.4930 Boehringer Ingelheim Investigational Site	Freiburg		Germany
123	1100.1486.4909 Boehringer Ingelheim Investigational Site	Hamburg		Germany
124	1100.1486.4920 Boehringer Ingelheim Investigational Site	Hamburg		Germany
125	1100.1486.4925 Boehringer Ingelheim Investigational Site	Hamburg		Germany
126	1100.1486.4915 Boehringer Ingelheim Investigational Site	Hannover		Germany
127	1100.1486.4923 Boehringer Ingelheim Investigational Site	Hannover		Germany
128	1100.1486.4910 Boehringer Ingelheim Investigational Site	Kiel		Germany
129	1100.1486.4907 Boehringer Ingelheim Investigational Site	Köln		Germany
130	1100.1486.4924 Boehringer Ingelheim Investigational Site	Köln		Germany
131	1100.1486.4927 Boehringer Ingelheim Investigational Site	Mainz		Germany
132	1100.1486.4903 Boehringer Ingelheim Investigational Site	München		Germany
133	1100.1486.4904 Boehringer Ingelheim Investigational Site	München		Germany
134	1100.1486.4912 Boehringer Ingelheim Investigational Site	München		Germany
135	1100.1486.4905 Boehringer Ingelheim Investigational Site	Münster		Germany
136	1100.1486.4918 Boehringer Ingelheim Investigational Site	Osnabrück		Germany
137	1100.1486.4913 Boehringer Ingelheim Investigational Site	Ulm/Donau		Germany
138	1100.1486.4914 Boehringer Ingelheim Investigational Site	Würzburg		Germany
139	1100.1486.3531 Boehringer Ingelheim Investigational Site	Dublin 8		Ireland
140	1100.1486.3532 Boehringer Ingelheim Investigational Site	Dublin		Ireland
141	1100.1486.3908 Boehringer Ingelheim Investigational Site	Palermo		Italy
142	1100.1486.3905 Boehringer Ingelheim Investigational Site	Pescara		Italy
143	1100.1486.3901 Boehringer Ingelheim Investigational Site	Torino		Italy
144	1100.1486.3907 Boehringer Ingelheim Investigational Site	Treviso		Italy
145	1100.1486.3906 Boehringer Ingelheim Investigational Site	Verbania		Italy
146	1100.1486.5207 Boehringer Ingelheim Investigational Site	Guadalajara		Mexico
147	1100.1486.5204 Boehringer Ingelheim Investigational Site	León		Mexico
148	1100.1486.3107 Boehringer Ingelheim Investigational Site	Amsterdam		Netherlands
149	1100.1486.3103 Boehringer Ingelheim Investigational Site	Arnhem		Netherlands
150	1100.1486.3101 Boehringer Ingelheim Investigational Site	Rotterdam		Netherlands
151	1100.1486.3102 Boehringer Ingelheim Investigational Site	Zwolle		Netherlands
152	1100.1486.4803 Boehringer Ingelheim Investigational Site	Bydgoszcz		Poland
153	1100.1486.4801 Boehringer Ingelheim Investigational Site	Chorzow		Poland
154	1100.1486.4804 Boehringer Ingelheim Investigational Site	Warsaw		Poland
155	1100.1486.3503 Boehringer Ingelheim Investigational Site	Amadora		Portugal
156	1100.1486.3501 Boehringer Ingelheim Investigational Site	Lisboa		Portugal
157	1100.1486.3504 Boehringer Ingelheim Investigational Site	Lisboa		Portugal
158	1100.1486.0024 Boehringer Ingelheim Investigational Site	Ponce		Puerto Rico
159	1100.1486.0033 Boehringer Ingelheim Investigational Site	San Juan		Puerto Rico
160	1100.1486.4001 Boehringer Ingelheim Investigational Site	Bucharest		Romania
161	1100.1486.4002 Boehringer Ingelheim Investigational Site	Bucharest		Romania
162	1100.1486.7002 Boehringer Ingelheim Investigational Site	Moscow		Russian Federation
163	1100.1486.7001 Boehringer Ingelheim Investigational Site	St. Petersburg		Russian Federation
164	1100.1486.2707 Boehringer Ingelheim Investigational Site	Bloemfontein		South Africa
165	1100.1486.2712 Boehringer Ingelheim Investigational Site	Bloemfontein		South Africa
166	1100.1486.2703 Boehringer Ingelheim Investigational Site	Cape Town		South Africa
167	1100.1486.2709 Boehringer Ingelheim Investigational Site	Cape Town		South Africa
168	1100.1486.2711 Boehringer Ingelheim Investigational Site	Cape Town		South Africa
169	1100.1486.2701 Boehringer Ingelheim Investigational Site	Edenvale		South Africa
170	1100.1486.2710 Boehringer Ingelheim Investigational Site	Johannesburg		South Africa
171	1100.1486.2706 Boehringer Ingelheim Investigational Site	Nelspruit		South Africa
172	1100.1486.2702 Boehringer Ingelheim Investigational Site	Port Elizabeth		South Africa
173	1100.1486.2704 Boehringer Ingelheim Investigational Site	Pretoria		South Africa
174	1100.1486.3406 Boehringer Ingelheim Investigational Site	Alcalá de Henares (Madrid)		Spain
175	1100.1486.3401 Boehringer Ingelheim Investigational Site	Barcelona		Spain
176	1100.1486.3402 Boehringer Ingelheim Investigational Site	Barcelona		Spain
177	1100.1486.3410 Boehringer Ingelheim Investigational Site	Barcelona		Spain
178	1100.1486.3415 Boehringer Ingelheim Investigational Site	Barcelona		Spain
179	1100.1486.3417 Boehringer Ingelheim Investigational Site	Barcelona		Spain
180	1100.1486.3404 Boehringer Ingelheim Investigational Site	L'Hospitalet de Llobregat		Spain
181	1100.1486.3403 Boehringer Ingelheim Investigational Site	Madrid		Spain
182	1100.1486.3405 Boehringer Ingelheim Investigational Site	Madrid		Spain
183	1100.1486.3407 Boehringer Ingelheim Investigational Site	Madrid		Spain
184	1100.1486.3414 Boehringer Ingelheim Investigational Site	Madrid		Spain
185	1100.1486.3416 Boehringer Ingelheim Investigational Site	Mataro		Spain
186	1100.1486.3408 Boehringer Ingelheim Investigational Site	Valencia		Spain
187	1100.1486.4101 Boehringer Ingelheim Investigational Site	Basel		Switzerland
188	1100.1486.4109 Boehringer Ingelheim Investigational Site	Bern		Switzerland
189	1100.1486.4107 Boehringer Ingelheim Investigational Site	Genève		Switzerland
190	1100.1486.4106 Boehringer Ingelheim Investigational Site	La Chaux-de-Fonds		Switzerland
191	1100.1486.4104 Boehringer Ingelheim Investigational Site	Lausanne		Switzerland
192	1100.1486.4102 Boehringer Ingelheim Investigational Site	Lugano		Switzerland
193	1100.1486.4108 Boehringer Ingelheim Investigational Site	St. Gallen		Switzerland
194	1100.1486.4110 Boehringer Ingelheim Investigational Site	Zürich		Switzerland
195	1100.1486.4406 Boehringer Ingelheim Investigational Site	Birmingham		United Kingdom
196	1100.1486.4403 Boehringer Ingelheim Investigational Site	London		United Kingdom
197	1100.1486.4404 Boehringer Ingelheim Investigational Site	London		United Kingdom
198	1100.1486.4405 Boehringer Ingelheim Investigational Site	London		United Kingdom
199	1100.1486.4407 Boehringer Ingelheim Investigational Site	London		United Kingdom
200	1100.1486.4401 Boehringer Ingelheim Investigational Site	Manchester		United Kingdom
201	1100.1486.4408 Boehringer Ingelheim Investigational Site	Manchester		United Kingdom
202	1100.1486.4402 Boehringer Ingelheim Investigational Site	Plaistow, London		United Kingdom

Sponsors and Collaborators

• Boehringer Ingelheim

Investigators

• Study Chair: Boehringer Ingelheim, Boehringer Ingelheim

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: Boehringer Ingelheim
• ClinicalTrials.gov Identifier: NCT00561925
• Other Study ID Numbers: 1100.1486; 2007-003654-29
• First Posted: Nov 21, 2007
• Last Update Posted: Apr 7, 2014
• Last Verified: Mar 1, 2014

• Additional relevant MeSH terms: HIV Infections; Nevirapine

Study Results

Participant Flow

Arm/Group Title	NVP IR 200mg QD	NVP IR 200mg BID	NVP XR 400mg QD	NVP XR	NVP IR to XR
Arm/Group Description	Nevirapine immediate release 200 mg given once daily	Nevirapine immediate release 200 mg given twice daily	Nevirapine extended release 400 mg given once daily
Period Title: 14 Day Lead-In Period
STARTED	1068	0	0	0	0
COMPLETED	1013	0	0	0	0
NOT COMPLETED	55	0	0	0	0
Period Title: 14 Day Lead-In Period
STARTED	0	508	505	0	0
COMPLETED	0	358	378	0	0
NOT COMPLETED	0	150	127	0	0
Period Title: 14 Day Lead-In Period
STARTED	0	1	0	358	378
COMPLETED	0	1	0	315	328
NOT COMPLETED	0	0	0	43	50

Baseline Characteristics

Arm/Group Title	NVP IR 200mg QD	NVP IR 200mg BID	NVP XR 400mg QD	Total
Arm/Group Description	Nevirapine immediate release 200 mg tablets given once daily	Nevirapine immediate release 200 mg tablets given twice daily	Nevirapine extended release 400 mg tablets given once daily	Total of all reporting groups
Overall Participants	0	508	505	1013
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	38.0 (9.7)	38.3 (9.7)	38.1 (9.7)
Age, Customized (participants) [Number]
18 to < 41 years	316 Infinity	299 58.9%	615 121.8%
41 to < 56 years	165 Infinity	182 35.8%	347 68.7%
56 to < 65 years	25 Infinity	19 3.7%	44 8.7%
65 years or more	2 Infinity	5 1%	7 1.4%
Gender (participants) [Number]
Female	75 Infinity	74 14.6%	149 29.5%
Male	433 Infinity	431 84.8%	864 171.1%
Race/Ethnicity, Customized (participants) [Number]
American Indian / Alaskan Native	6 Infinity	8 1.6%	14 2.8%
Asian	13 Infinity	15 3%	28 5.5%
Black	113 Infinity	94 18.5%	207 41%
Hawaiian / Pacific Isle.	0 NaN	1 0.2%	1 0.2%
White	376 Infinity	387 76.2%	763 151.1%
Race/Ethnicity, Customized (Number) [Number]
Hispanic / Latino	109 Infinity	115 22.6%	224 44.4%
Not Hispanic / Latino	399 Infinity	390 76.8%	789 156.2%
Region of Enrollment (participants) [Number]
North America / Australia	149 Infinity	141 27.8%	290 57.4%
Europe	253 Infinity	257 50.6%	510 101%
Latin America	49 Infinity	58 11.4%	107 21.2%
Africa	57 Infinity	49 9.6%	106 21%
Smoking History (participants) [Number]
Never smoked	250 Infinity	224 44.1%	474 93.9%
Ex-smoker	81 Infinity	86 16.9%	167 33.1%
Current smoker	177 Infinity	195 38.4%	372 73.7%
Alcohol Status (participants) [Number]
Non drinker	151 Infinity	168 33.1%	319 63.2%
Drinks - no interfere with trial	354 Infinity	335 65.9%	689 136.4%
Drinks - could interfere with trial	3 Infinity	2 0.4%	5 1%

Outcome Measures

1. Primary Outcome

Title	Comparison of Proportion of Virologic Response at Week 48 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population
Description	Primary endpoint was the number of patients with a sustained virologic response through week 48 using LLOQ = 50 copies/mL
Time Frame	week 48

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication

Arm/Group Title	NVP IR 200mg QD	NVP IR 200mg BID	NVP XR 400mg QD
Arm/Group Description	Nevirapine immediate release 200 mg tablets given once daily	Nevirapine immediate release 200 mg tablets given twice daily	Nevirapine extended release 400 mg tablets given once daily
Measure Participants	0	506	505
Responder	384 Infinity	409 80.5%
Non responder	122 Infinity	96 18.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NVP IR 200mg BID, NVP XR 400mg QD
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority of nevirapine XR to nevirapine IR was established if the lower bound of the confidence interval was greater than -10%
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran's statistic
	Comments
Method of Estimation	Estimation Parameter	Cochran's statistic
	Estimated Value	4.9
	Confidence Interval	() 95%; -0.1 to 10.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Weighted treatment difference and corresponding variance were calculated based on Cochran's statistic.

2. Secondary Outcome

Title	Kaplan-Meier Estimates of the Proportions of Patients Without Loss of Virologic Response Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population
Time Frame	week 0 to 144

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication

Arm/Group Title	NVP IR 200mg QD	NVP IR 200mg BID	NVP XR 400mg QD
Arm/Group Description	Nevirapine immediate release 200 mg tablets given once daily	Nevirapine immediate release 200 mg tablets given twice daily	Nevirapine extended release 400 mg tablets given once daily
Measure Participants	0	506	505
Interval Week 0 to <2	1 Infinity	1 0.2%
Interval Week 2 to <4	0.84 Infinity	0.865 0.2%
Interval Week 4 to <6	0.838 Infinity	0.865 0.2%
Interval Week 6 to <8	0.834 Infinity	0.865 0.2%
Interval Week 8 to <12	0.834 Infinity	0.863 0.2%
Interval Week 12 to <16	0.832 Infinity	0.861 0.2%
Interval Week 16 to <24	0.83 Infinity	0.859 0.2%
Interval Week 24 to <32	0.822 Infinity	0.848 0.2%
Interval Week 32 to <40	0.806 Infinity	0.832 0.2%
Interval Week 40 to <48	0.792 Infinity	0.816 0.2%
Interval Week 48 to <60	0.777 Infinity	0.808 0.2%
Interval Week 60 to <72	0.759 Infinity	0.788 0.2%
Interval Week 72 to <84	0.733 Infinity	0.766 0.2%
Interval Week 84 to <96	0.713 Infinity	0.745 0.1%
Interval Week 96 to <108	0.686 Infinity	0.719 0.1%
Interval Week 108 to <120	0.662 Infinity	0.697 0.1%
Interval Week 120 to <132	0.65 Infinity	0.681 0.1%
Interval Week 132 to <144	0.63 Infinity	0.671 0.1%
Interval Week 144 to <168	0.61 Infinity	0.66 0.1%

3. Secondary Outcome

Title	Proportion of Sustained Virologic Response at Week 144 Using Lower Limit of Quantification (LLOQ) = 50 Copies/mL, Full Analysis Set Population
Description	Endpoint was the number of patients with a sustained virologic response through week 144 using LLOQ = 50 copies/mL
Time Frame	week 144

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication

Arm/Group Title	NVP IR 200mg QD	NVP IR 200mg BID	NVP XR 400mg QD
Arm/Group Description	Nevirapine immediate release 200 mg tablets given once daily	Nevirapine immediate release 200 mg tablets given twice daily	Nevirapine extended release 400 mg tablets given once daily
Measure Participants	0	506	505
Responder	296 Infinity	321 63.2%
Non responder	210 Infinity	184 36.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NVP IR 200mg BID, NVP XR 400mg QD
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Non-inferiority of nevirapine XR to nevirapine IR was established if the lower bound of the confidence interval was greater than -2%
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran's statistic
	Comments
Method of Estimation	Estimation Parameter	Cochran's statistic
	Estimated Value	4.84
	Confidence Interval	() 95%; -1.11 to 10.79
	Parameter Dispersion	Type: Value:
	Estimation Comments	Weighted treatment difference and corresponding variance were calculated based on Cochran's statistic.

4. Secondary Outcome

Title	Kaplan-Meier Estimates for Time to New AIDS or AIDS-related Progression Event or Death, Full Analysis Set Population
Time Frame	week 0 to 144

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication

Arm/Group Title	NVP IR 200mg QD	NVP IR 200mg BID	NVP XR 400mg QD
Arm/Group Description	Nevirapine immediate release 200 mg tablets given once daily	Nevirapine immediate release 200 mg tablets given twice daily	Nevirapine extended release 400 mg tablets given once daily
Measure Participants	0	506	505
Interval Week 0 to <2	0 NaN	0 0%
Interval Week 2 to <4	0.006 Infinity	0.002 0%
Interval Week 4 to <6	0.006 Infinity	0.006 0%
Interval Week 6 to <8	0.023 Infinity	0.008 0%
Interval Week 8 to <12	0.029 Infinity	0.01 0%
Interval Week 12 to <16	0.029 Infinity	0.019 0%
Interval Week 16 to <24	0.031 Infinity	0.021 0%
Interval Week 24 to <32	0.04 Infinity	0.025 0%
Interval Week 32 to <40	0.042 Infinity	0.025 0%
Interval Week 40 to <48	0.047 Infinity	0.027 0%
Interval Week 48 to <60	0.047 Infinity	0.027 0%
Interval Week 60 to <72	0.052 Infinity	0.032 0%
Interval Week 72 to <84	0.054 Infinity	0.035 0%
Interval Week 84 to <96	0.054 Infinity	0.04 0%
Interval Week 96 to <108	0.057 Infinity	0.04 0%
Interval Week 108 to <120	0.057 Infinity	0.045 0%
Interval Week 120 to <132	0.06 Infinity	0.047 0%
Interval Week 132 to <144	0.06 Infinity	0.047 0%
Interval Week 144 to <168	0.062 Infinity	0.047 0%

5. Secondary Outcome

Title	Comparison of HIV-1 Viral Load (log10 Copies/mL) Change From Baseline at Week 144, Full Analysis Set Population
Time Frame	baseline, week 144

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication; descriptive analysis uses the imputation method: last observation carried forward; statistical analysis uses observed cases

Arm/Group Title	NVP IR 200mg QD	NVP IR 200mg BID	NVP XR 400mg QD
Arm/Group Description	Nevirapine immediate release 200 mg tablets given once daily	Nevirapine immediate release 200 mg tablets given twice daily	Nevirapine extended release 400 mg tablets given once daily
Measure Participants	0	506	505
Mean (Standard Deviation) [log10 copies/mL]	-2.7 (0.9)	-2.8 (0.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NVP IR 200mg BID, NVP XR 400mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7719
	Comments
	Method	ANCOVA
	Comments	Means adjusted for baseline HIV-1 viral load stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.01
	Confidence Interval	() 95%; -0.08 to 0.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Comparison of CD4+ Cell Count (Cells/Cubic Millimeter) Change From Baseline at Week 144, Full Analysis Set Population
Time Frame	baseline, week 144

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication; descriptive analysis uses the imputation method: last observation carried forward; statistical analysis uses observed cases

Arm/Group Title	NVP IR 200mg QD	NVP IR 200mg BID	NVP XR 400mg QD
Arm/Group Description	Nevirapine immediate release 200 mg tablets given once daily	Nevirapine immediate release 200 mg tablets given twice daily	Nevirapine extended release 400 mg tablets given once daily
Measure Participants	0	506	505
Mean (Standard Deviation) [cells/cubic millimeter]	239.3 (171.4)	270.7 (183.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NVP IR 200mg BID, NVP XR 400mg QD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0078
	Comments
	Method	ANCOVA
	Comments	Means adjusted for baseline HIV-1 viral load stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	32.87
	Confidence Interval	() 95%; 8.67 to 57.06
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Occurrence of Rashes
Description	Frequency of patients with drug related rash events by functional grouping
Time Frame	until last patient completed 144 weeks (up to 193 weeks)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication

Arm/Group Title	NVP IR	NVP XR	IR-IR/XR	XR-IR/XR
Arm/Group Description	Patients received nevirapine IR during the 144 week blinded phase and nevirapine XR during open label extension	Patients receiving nevirapine XR during the 144 week blinded phase and nevirapine XR during open label extension	Patients receiving nevirapine IR during the 144 week blinded phase and then receiving nevirapine XR in the post week 144 of extension	Patients receiving nevirapine XR during open label extension and previously receiving nevirapine IR during the pre week 144
Measure Participants	191	505	315	315
rash group I	9 Infinity	11 2.2%	6 1.2%	0 0%
rash group II	6 Infinity	13 2.6%	3 0.6%	0 0%
rash group IIA	4 Infinity	5 1%	1 0.2%	0 0%
rash group III	3 Infinity	5 1%	0 0%	0 0%
rash group IV	0 NaN	0 0%	0 0%	0 0%

8. Secondary Outcome

Title	Occurrence of Elevations in Laboratory Measurement by DAIDS Grade
Time Frame	until last patient completed 144 weeks (up to 193 weeks)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication

Arm/Group Title	NVP IR	NVP XR	IR-IR/XR	XR-IR/XR
Arm/Group Description	Patients received nevirapine IR during the 144 week blinded phase and nevirapine XR during open label extension	Patients receiving nevirapine XR during the 144 week blinded phase and nevirapine XR during open label extension	Patients receiving nevirapine IR during the 144 week blinded phase and then receiving nevirapine XR in the post week 144 of extension	Patients receiving nevirapine XR during open label extension and previously receiving nevirapine IR during the pre week 144
Measure Participants	191	505	315	315
DAIDS grade 3 or 4 AEs	53 Infinity	111 21.9%	71 14.1%	8 0.8%
DAIDS grade 4 AEs	17 Infinity	25 4.9%	11 2.2%	3 0.3%

9. Secondary Outcome

Title	Kaplan -Meier Estimate of Cumulative Probability of Permanent Discontinuation of Study Medication
Time Frame	week 0 to 144

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication

Arm/Group Title	NVP IR	NVP XR
Arm/Group Description	Nevirapine immediate release 200 mg tablets given twice daily	Nevirapine extended release 400 mg tablets given once daily
Measure Participants	506	505
Interval Week 0 to <2	0.000	0.000
Interval Week 2 to <4	0.000	0.000
Interval Week 4 to <6	0.034	0.026
Interval Week 6 to <8	0.067	0.046
Interval Week 8 to <12	0.081	0.059
Interval Week 12 to <16	0.093	0.067
Interval Week 16 to <24	0.113	0.083
Interval Week 24 to <32	0.130	0.115
Interval Week 32 to <40	0.156	0.139
Interval Week 40 to <48	0.172	0.156
Interval Week 48 to <60	0.192	0.162
Interval Week 60 to <72	0.202	0.176
Interval Week 72 to <84	0.213	0.188
Interval Week 84 to <96	0.229	0.206
Interval Week 96 to <108	0.243	0.218
Interval Week 108 to <120	0.267	0.232
Interval Week 120 to <132	0.275	0.236
Interval Week 132 to <144	0.289	0.244

10. Secondary Outcome

Title	Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 ALT/AST Abnormalities
Time Frame	week 0 to 72

Outcome Measure Data

Analysis Population Description

Treated set (TS) includes all patients who were dispensed study medication and were documented to have taken at least one doe of investigational treatment, including the lead in nevirapine dose

Arm/Group Title	NVP IR	NVP XR
Arm/Group Description	Nevirapine immediate release 200 mg tablets given twice daily	Nevirapine extended release 400 mg tablets given once daily
Measure Participants	506	505
Interval Week 0 to <2	0.000	0.000
Interval Week 2 to <4	0.000	0.002
Interval Week 4 to <6	0.012	0.014
Interval Week 6 to <8	0.049	0.026
Interval Week 8 to <12	0.059	0.034
Interval Week 12 to <16	0.063	0.036
Interval Week 16 to <24	0.063	0.036
Interval Week 24 to <32	0.067	0.043
Interval Week 32 to <40	0.070	0.049
Interval Week 40 to <48	0.076	0.056
Interval Week 48 to <60	0.076	0.058
Interval Week 60 to <72	0.076	0.058
Interval Week >=72	0.076	0.070

11. Secondary Outcome

Title	Kaplan -Meier Estimate of Cumulative Probability of Grade 3 or 4 Asymptotic Transaminases Abnormalities
Time Frame	week 0 to 72

Outcome Measure Data

Analysis Population Description

Treated set (TS) includes all patients who were dispensed study medication and were documented to have taken at least one doe of investigational treatment, including the lead in nevirapine dose

Arm/Group Title	NVP IR	NVP XR
Arm/Group Description	Nevirapine immediate release 200 mg tablets given twice daily	Nevirapine extended release 400 mg tablets given once daily
Measure Participants	506	505
Interval Week 0 to <2	0.000	0.000
Interval Week 2 to <4	0.000	0.000
Interval Week 4 to <6	0.006	0.002
Interval Week 6 to <8	0.027	0.006
Interval Week 8 to <12	0.033	0.008
Interval Week 12 to <16	0.039	0.008
Interval Week 16 to <24	0.039	0.008
Interval Week 24 to <32	0.042	0.015
Interval Week 32 to <40	0.044	0.019
Interval Week 40 to <48	0.053	0.028
Interval Week 48 to <60	0.053	0.031
Interval Week 60 to <72	0.053	0.033
Interval Week >=72	0.053	0.033

12. Secondary Outcome

Title	Kaplan -Meier Estimate of Cumulative Probability of Clinical Hepatic Events
Time Frame	week 0 to 72

Outcome Measure Data

Analysis Population Description

Treated set (TS) includes all patients who were dispensed study medication and were documented to have taken at least one doe of investigational treatment, including the lead in nevirapine dose

Arm/Group Title	NVP IR	NVP XR
Arm/Group Description	Nevirapine immediate release 200 mg tablets given twice daily	Nevirapine extended release 400 mg tablets given once daily
Measure Participants	506	505
Interval Week 0 to <2	0.000	0.000
Interval Week 2 to <4	0.000	0.002
Interval Week 4 to <6	0.012	0.010
Interval Week 6 to <8	0.022	0.016
Interval Week 8 to <12	0.024	0.018
Interval Week 12 to <16	0.026	0.018
Interval Week 16 to <24	0.026	0.018
Interval Week 24 to <32	0.026	0.020
Interval Week 32 to <40	0.026	0.022
Interval Week 40 to <48	0.029	0.022
Interval Week 48 to <60	0.029	0.022
Interval Week 60 to <72	0.032	0.022
Interval Week >=72	0.038	0.026

13. Secondary Outcome

Title	Kaplan -Meier Estimate of Cumulative Probability of Group III or IV Drug-related Rash
Time Frame	week 0 to 72

Outcome Measure Data

Analysis Population Description

Treated set (TS) includes all patients who were dispensed study medication and were documented to have taken at least one doe of investigational treatment, including the lead in nevirapine dose

Arm/Group Title	NVP IR	NVP XR
Arm/Group Description	Nevirapine immediate release 200 mg tablets given twice daily	Nevirapine extended release 400 mg tablets given once daily
Measure Participants	506	505
Interval Week 0 to <2	0.000	0.000
Interval Week 2 to <4	0.000	0.000
Interval Week 4 to <6	0.002	0.006
Interval Week 6 to <8	0.004	0.008
Interval Week 8 to <12	0.004	0.010
Interval Week 12 to <16	0.004	0.010
Interval Week 16 to <24	0.004	0.010
Interval Week 24 to <32	0.004	0.010
Interval Week 32 to <40	0.004	0.010
Interval Week 40 to <48	0.004	0.010
Interval Week 48 to <60	0.004	0.010
Interval Week 60 to <72	0.004	0.010
Interval Week >=72	0.004	0.010

14. Secondary Outcome

Title	Relative Bioavailability Trough C_pre,ss,1
Description	Relative bioavailability measured of trough concentrations. Analysis based on adjusted by-treatment geometric means, the adjusted geometric mean ratio of NVP XR : NVP IR and it's 90% confidence interval with p-value and the inter-individual geometric coefficient of variation.
Time Frame	week 132

Outcome Measure Data

Analysis Population Description

Only patients with trough drawn PK time window (12+/-2.5 hr for IR; 24+/-5hr for XR) at week 132 are included.

Arm/Group Title	NVP IR	NVP XR
Arm/Group Description	Nevirapine immediate release 200 mg tablets given twice daily	Nevirapine extended release 400 mg tablets given once daily
Measure Participants	276	311
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	4567.03 (49.9)	3634.26 (49.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	NVP IR 200mg QD, NVP IR 200mg BID
	Comments	adjusted geometric mean ratio NVP XR : NVP IR
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	equivalence test with 80% -125% boundaries
Statistical Test of Hypothesis	p-Value	0.5542
	Comments	p-value for ratio outside the interval 80%-125%
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	adjusted gMean
	Estimated Value	79.58
	Confidence Interval	() 90%; 74.62 to 84.86
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.04
	Estimation Comments	Inter-individual gCV = 49.9

15. Secondary Outcome

Title	Occurrence of Hepatic Events
Description	Frequency of patients with hepatitis symptoms
Time Frame	until last patient completed 144 weeks (up to 193 weeks)

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) includes all participants randomized to treatment and confirmed to have taken at least one dose of blinded medication

Arm/Group Title	NVP IR	NVP XR	IR-IR/XR	XR-IR/XR
Arm/Group Description	Patients received nevirapine IR during the 144 week blinded phase but who never took nevirapine XR during the open label extension	Patients receiving nevirapine XR during the 144 week blinded phase and nevirapine XR during open label extension	Patients receiving nevirapine IR during the 144 week blinded phase and then receiving nevirapine XR in the post week 144 of extension	Patients receiving nevirapine XR during open label extension who had previously received nevirapine IR during the pre week 144
Measure Participants	191	505	315	315
Number [participants]	10 Infinity	8 1.6%	2 0.4%	0 0%

Adverse Events

Time Frame	Up to 193 weeks
Adverse Event Reporting Description	Safety data in this report included all the patient visits up to the point in time when the last patient completed 144 weeks in the trial. This also includes safety data for patient visits in the post week 144 open label extension which patients in either treatment group who completed the 144 week blinded phase could enter (see also Limitation).
Arm/Group Title	NVP IR 200mg QD		NVP IR		NVP XR		NVP IR-IR/XR		NVP XR-IR/XR
Arm/Group Description	Nevirapine immediate release 200 mg given once daily		Patients received nevirapine IR during the 144 week blinded phase but who never took nevirapine XR during the open label extension		Patients receiving nevirapine XR during the 144 week blinded phase and nevirapine XR during open label extension		Patients receiving nevirapine IR during the 144 week blinded phase and then receiving nevirapine XR in the post week 144 of extension		Patients receiving nevirapine XR during open label extension who had previously receiving nevirapine IR during the pre week 144
All Cause Mortality
	NVP IR 200mg QD		NVP IR		NVP XR		NVP IR-IR/XR		NVP XR-IR/XR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	NVP IR 200mg QD		NVP IR		NVP XR		NVP IR-IR/XR		NVP XR-IR/XR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/1068 (1.9%)		33/191 (17.3%)		93/505 (18.4%)		50/315 (15.9%)		9/315 (2.9%)
Blood and lymphatic system disorders
Anaemia	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Neutropenia	1/1068 (0.1%)		0/191 (0%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Normochromic normocytic anaemia	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Cardiac disorders
Acute myocardial infarction	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Atrioventricular block	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Cardiac failure congestive	0/1068 (0%)		0/191 (0%)		2/505 (0.4%)		0/315 (0%)		0/315 (0%)
Mitral valve incompetence	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Myocardial infarction	0/1068 (0%)		1/191 (0.5%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Pericardial effusion	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Pericardial rub	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Pericarditis	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Supraventricular tachycardia	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Endocrine disorders
Hyperthyroidism	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Eye disorders
Retinal detachment	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		1/315 (0.3%)		1/315 (0.3%)
Strabismus	0/1068 (0%)		0/191 (0%)		0/505 (0%)		0/315 (0%)		1/315 (0.3%)
Gastrointestinal disorders
Anal fissure	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Colitis	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Diarrhoea	0/1068 (0%)		0/191 (0%)		0/505 (0%)		0/315 (0%)		1/315 (0.3%)
Enterocolitis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Gastritis	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Gastrooesophageal reflux disease	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Haemorrhoids	0/1068 (0%)		0/191 (0%)		2/505 (0.4%)		0/315 (0%)		0/315 (0%)
Inguinal hernia	1/1068 (0.1%)		0/191 (0%)		2/505 (0.4%)		0/315 (0%)		0/315 (0%)
Intestinal obstruction	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Nausea	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Oral disorder	1/1068 (0.1%)		0/191 (0%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Pancreatitis chronic	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Peritoneal adhesions	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Proctitis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		2/315 (0.6%)		0/315 (0%)
Retroperitoneal fibrosis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Umbilical hernia	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Vomiting	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
General disorders
Face oedema	1/1068 (0.1%)		0/191 (0%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Gait disturbance	1/1068 (0.1%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Hyperplasia	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Influenza like illness	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Polyserositis	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Pyrexia	2/1068 (0.2%)		0/191 (0%)		1/505 (0.2%)		1/315 (0.3%)		1/315 (0.3%)
Hepatobiliary disorders
Biliary colic	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Cholelithiasis	0/1068 (0%)		1/191 (0.5%)		2/505 (0.4%)		1/315 (0.3%)		0/315 (0%)
Cytolytic hepatitis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Hepatic failure	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Hepatic necrosis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Hepatitis	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Hepatitis acute	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Hepatitis toxic	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Hepatotoxicity	0/1068 (0%)		2/191 (1%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Immune system disorders
Drug hypersensitivity	1/1068 (0.1%)		0/191 (0%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Hypersensitivity	1/1068 (0.1%)		0/191 (0%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Infections and infestations
AIDS encephalopathy	0/1068 (0%)		0/191 (0%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Abdominal abscess	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Abscess	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Abscess intestinal	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Abscess limb	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Anal abscess	1/1068 (0.1%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Appendicitis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		2/315 (0.6%)		0/315 (0%)
Appendicitis perforated	0/1068 (0%)		1/191 (0.5%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Arthritis bacterial	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Bronchitis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		1/315 (0.3%)		0/315 (0%)
Bronchopneumonia	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Candidiasis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Cellulitis	0/1068 (0%)		1/191 (0.5%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Cerebral toxoplasmosis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Chronic sinusitis	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Endocarditis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Enteritis infectious	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Enterocolitis infectious	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Epiglottitis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Erysipelas	0/1068 (0%)		0/191 (0%)		2/505 (0.4%)		0/315 (0%)		0/315 (0%)
Eye infection syphilitic	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Furuncle	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Gastroenteritis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		2/315 (0.6%)		0/315 (0%)
Gastroenteritis viral	1/1068 (0.1%)		0/191 (0%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Giardiasis	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Groin abscess	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
H1N1 influenza	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Hepatitis A	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Herpes simplex	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Herpes zoster disseminated	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Laryngitis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Lobar pneumonia	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Lung abscess	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Meningitis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Meningitis bacterial	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Meningitis cryptococcal	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Meningitis histoplasma	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Meningitis tuberculous	1/1068 (0.1%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Meningitis viral	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Neurocryptococcosis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Orchitis	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Pilonidal cyst	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Pneumonia	0/1068 (0%)		3/191 (1.6%)		7/505 (1.4%)		0/315 (0%)		0/315 (0%)
Pneumonia bacterial	1/1068 (0.1%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Pneumonia pneumococcal	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Pneumonia staphylococcal	1/1068 (0.1%)		0/191 (0%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Pulmonary tuberculosis	0/1068 (0%)		1/191 (0.5%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Rectal abscess	1/1068 (0.1%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Sepsis	0/1068 (0%)		1/191 (0.5%)		3/505 (0.6%)		0/315 (0%)		0/315 (0%)
Shigella infection	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		1/315 (0.3%)		0/315 (0%)
Sinusitis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Subcutaneous abscess	0/1068 (0%)		0/191 (0%)		0/505 (0%)		0/315 (0%)		1/315 (0.3%)
Syphilis	1/1068 (0.1%)		0/191 (0%)		2/505 (0.4%)		0/315 (0%)		0/315 (0%)
Tuberculosis	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Urinary tract infection	0/1068 (0%)		2/191 (1%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Wound sepsis	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Injury, poisoning and procedural complications
Alcohol poisoning	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Arthropod sting	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Burns second degree	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Concussion	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Contrast media reaction	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Contusion	0/1068 (0%)		1/191 (0.5%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Excoriation	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Fall	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		2/315 (0.6%)		0/315 (0%)
Foot fracture	0/1068 (0%)		0/191 (0%)		0/505 (0%)		3/315 (1%)		0/315 (0%)
Hand fracture	0/1068 (0%)		0/191 (0%)		2/505 (0.4%)		0/315 (0%)		0/315 (0%)
Head injury	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Humerus fracture	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Injury	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Intentional overdose	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Laceration	0/1068 (0%)		1/191 (0.5%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Ligament rupture	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Lower limb fracture	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Meniscus lesion	0/1068 (0%)		0/191 (0%)		0/505 (0%)		3/315 (1%)		0/315 (0%)
Multiple injuries	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Neck injury	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Overdose	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Poisoning	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Postoperative wound complication	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Road traffic accident	0/1068 (0%)		0/191 (0%)		3/505 (0.6%)		0/315 (0%)		0/315 (0%)
Stab wound	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Tendon rupture	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Thermal burn	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Tibia fracture	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Investigations
Alanine aminotransferase increased	0/1068 (0%)		1/191 (0.5%)		2/505 (0.4%)		0/315 (0%)		0/315 (0%)
Aspartate aminotransferase increased	0/1068 (0%)		1/191 (0.5%)		2/505 (0.4%)		0/315 (0%)		0/315 (0%)
Blood bilirubin increased	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Catheterisation cardiac normal	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Gamma-glutamyltransferase increased	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Hepatic enzyme increased	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Transaminases increased	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Metabolism and nutrition disorders
Dehydration	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Diabetic ketoacidosis	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Hypernatraemia	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Type 1 diabetes mellitus	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/1068 (0.1%)		0/191 (0%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Back pain	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Groin pain	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Intervertebral disc protrusion	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		1/315 (0.3%)
Osteoarthritis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Osteonecrosis	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Plica syndrome	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts	0/1068 (0%)		1/191 (0.5%)		3/505 (0.6%)		0/315 (0%)		0/315 (0%)
Astrocytoma	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Bladder cancer recurrent	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Bladder neoplasm	0/1068 (0%)		0/191 (0%)		0/505 (0%)		0/315 (0%)		1/315 (0.3%)
Bone neoplasm malignant	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Burkitt's lymphoma	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Epithelioid sarcoma	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Hodgkin's disease	0/1068 (0%)		0/191 (0%)		2/505 (0.4%)		0/315 (0%)		0/315 (0%)
Kaposi's sarcoma	0/1068 (0%)		3/191 (1.6%)		2/505 (0.4%)		0/315 (0%)		0/315 (0%)
Non-Hodgkin's lymphoma	0/1068 (0%)		0/191 (0%)		2/505 (0.4%)		0/315 (0%)		0/315 (0%)
Oesophageal carcinoma	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Osteosarcoma localised	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Prostate cancer	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Uterine carcinoma in situ	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Uterine leiomyoma	0/1068 (0%)		1/191 (0.5%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Nervous system disorders
Aphasia	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Cervical root pain	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Convulsion	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Disturbance in attention	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Encephalopathy	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Headache	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Hypoaesthesia	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Intracranial hypotension	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		1/315 (0.3%)		0/315 (0%)
Myelopathy	0/1068 (0%)		0/191 (0%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Paraparesis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Sciatica	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Syncope	0/1068 (0%)		0/191 (0%)		0/505 (0%)		0/315 (0%)		1/315 (0.3%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Abortion spontaneous incomplete	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Psychiatric disorders
Acute stress disorder	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Adjustment disorder	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		1/315 (0.3%)		0/315 (0%)
Aggression	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Agitation	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Alcohol abuse	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Anxiety	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Bipolar I disorder	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Completed suicide	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Delirium	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Depression	0/1068 (0%)		1/191 (0.5%)		4/505 (0.8%)		3/315 (1%)		0/315 (0%)
Drug abuse	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Major depression	0/1068 (0%)		0/191 (0%)		0/505 (0%)		2/315 (0.6%)		0/315 (0%)
Psychotic disorder	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		1/315 (0.3%)
Social phobia	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Suicidal ideation	0/1068 (0%)		1/191 (0.5%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Suicide attempt	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		1/315 (0.3%)		0/315 (0%)
Renal and urinary disorders
Dysuria	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Nephrolithiasis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Renal failure	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Renal failure acute	0/1068 (0%)		0/191 (0%)		2/505 (0.4%)		0/315 (0%)		0/315 (0%)
Renal injury	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Cervical dysplasia	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Epididymitis	1/1068 (0.1%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Haemorrhagic ovarian cyst	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Infertility female	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Menorrhagia	0/1068 (0%)		0/191 (0%)		2/505 (0.4%)		0/315 (0%)		0/315 (0%)
Vaginal haemorrhage	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Respiratory, thoracic and mediastinal disorders
Diaphragmatic hernia	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Dyspnoea	0/1068 (0%)		1/191 (0.5%)		2/505 (0.4%)		0/315 (0%)		0/315 (0%)
Pleurisy	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Pulmonary embolism	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Pulmonary oedema	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Respiratory alkalosis	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Skin and subcutaneous tissue disorders
Angioedema	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Drug rash with eosinophilia and systemic symptoms	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Erythema multiforme	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Hidradenitis	0/1068 (0%)		0/191 (0%)		0/505 (0%)		0/315 (0%)		1/315 (0.3%)
Rash	5/1068 (0.5%)		1/191 (0.5%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Stevens-Johnson syndrome	2/1068 (0.2%)		4/191 (2.1%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Social circumstances
Aborted pregnancy	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Alcohol use	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Surgical and medical procedures
Abortion induced	0/1068 (0%)		0/191 (0%)		2/505 (0.4%)		1/315 (0.3%)		1/315 (0.3%)
Inguinal hernia repair	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Removal of internal fixation	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Tooth extraction	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Vascular disorders
Arteriosclerosis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Deep vein thrombosis	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Hypertension	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Hypotension	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Peripheral arterial occlusive disease	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Phlebitis	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Secondary hypertension	0/1068 (0%)		1/191 (0.5%)		0/505 (0%)		0/315 (0%)		0/315 (0%)
Varicose vein	0/1068 (0%)		0/191 (0%)		1/505 (0.2%)		0/315 (0%)		0/315 (0%)
Venous thrombosis	0/1068 (0%)		0/191 (0%)		0/505 (0%)		1/315 (0.3%)		0/315 (0%)
Other (Not Including Serious) Adverse Events
	NVP IR 200mg QD		NVP IR		NVP XR		NVP IR-IR/XR		NVP XR-IR/XR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	308/1068 (28.8%)		131/191 (68.6%)		403/505 (79.8%)		271/315 (86%)		81/315 (25.7%)
Gastrointestinal disorders
Abdominal pain	8/1068 (0.7%)		7/191 (3.7%)		25/505 (5%)		25/315 (7.9%)		2/315 (0.6%)
Diarrhoea	27/1068 (2.5%)		27/191 (14.1%)		94/505 (18.6%)		63/315 (20%)		7/315 (2.2%)
Nausea	71/1068 (6.6%)		18/191 (9.4%)		38/505 (7.5%)		38/315 (12.1%)		3/315 (1%)
Vomiting	16/1068 (1.5%)		11/191 (5.8%)		35/505 (6.9%)		22/315 (7%)		1/315 (0.3%)
General disorders
Fatigue	40/1068 (3.7%)		10/191 (5.2%)		34/505 (6.7%)		28/315 (8.9%)		2/315 (0.6%)
Pyrexia	20/1068 (1.9%)		12/191 (6.3%)		25/505 (5%)		12/315 (3.8%)		2/315 (0.6%)
Infections and infestations
Bronchitis	7/1068 (0.7%)		12/191 (6.3%)		71/505 (14.1%)		35/315 (11.1%)		4/315 (1.3%)
Gastroenteritis	5/1068 (0.5%)		10/191 (5.2%)		36/505 (7.1%)		27/315 (8.6%)		2/315 (0.6%)
Herpes zoster	6/1068 (0.6%)		7/191 (3.7%)		26/505 (5.1%)		17/315 (5.4%)		1/315 (0.3%)
Influenza	5/1068 (0.5%)		9/191 (4.7%)		33/505 (6.5%)		25/315 (7.9%)		0/315 (0%)
Nasopharyngitis	10/1068 (0.9%)		17/191 (8.9%)		123/505 (24.4%)		87/315 (27.6%)		15/315 (4.8%)
Pharyngitis	5/1068 (0.5%)		7/191 (3.7%)		33/505 (6.5%)		23/315 (7.3%)		2/315 (0.6%)
Sinusitis	5/1068 (0.5%)		5/191 (2.6%)		37/505 (7.3%)		22/315 (7%)		2/315 (0.6%)
Syphilis	1/1068 (0.1%)		8/191 (4.2%)		28/505 (5.5%)		19/315 (6%)		7/315 (2.2%)
Upper respiratory tract infection	13/1068 (1.2%)		23/191 (12%)		83/505 (16.4%)		50/315 (15.9%)		12/315 (3.8%)
Urinary tract infection	2/1068 (0.2%)		4/191 (2.1%)		26/505 (5.1%)		12/315 (3.8%)		5/315 (1.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/1068 (0.4%)		9/191 (4.7%)		33/505 (6.5%)		25/315 (7.9%)		9/315 (2.9%)
Back pain	7/1068 (0.7%)		5/191 (2.6%)		40/505 (7.9%)		30/315 (9.5%)		8/315 (2.5%)
Pain in extremity	4/1068 (0.4%)		5/191 (2.6%)		16/505 (3.2%)		20/315 (6.3%)		2/315 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anogenital warts	4/1068 (0.4%)		3/191 (1.6%)		29/505 (5.7%)		16/315 (5.1%)		0/315 (0%)
Skin papilloma	3/1068 (0.3%)		4/191 (2.1%)		19/505 (3.8%)		16/315 (5.1%)		1/315 (0.3%)
Nervous system disorders
Headache	58/1068 (5.4%)		18/191 (9.4%)		61/505 (12.1%)		55/315 (17.5%)		3/315 (1%)
Psychiatric disorders
Anxiety	5/1068 (0.5%)		7/191 (3.7%)		20/505 (4%)		16/315 (5.1%)		2/315 (0.6%)
Depression	8/1068 (0.7%)		7/191 (3.7%)		37/505 (7.3%)		31/315 (9.8%)		6/315 (1.9%)
Insomnia	8/1068 (0.7%)		9/191 (4.7%)		27/505 (5.3%)		19/315 (6%)		1/315 (0.3%)
Respiratory, thoracic and mediastinal disorders
Cough	11/1068 (1%)		14/191 (7.3%)		52/505 (10.3%)		36/315 (11.4%)		3/315 (1%)
Oropharyngeal pain	6/1068 (0.6%)		3/191 (1.6%)		30/505 (5.9%)		13/315 (4.1%)		3/315 (1%)
Skin and subcutaneous tissue disorders
Rash	74/1068 (6.9%)		26/191 (13.6%)		56/505 (11.1%)		25/315 (7.9%)		2/315 (0.6%)
Vascular disorders
Hypertension	5/1068 (0.5%)		13/191 (6.8%)		38/505 (7.5%)		22/315 (7%)		3/315 (1%)

Limitations/Caveats

For the lead-in-period with NVP IR 200mg QD, MedDRA Version 12.1 was used for AE/SAE reporting.

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Any publication of the result of this trial must be consistent with the Boehringer Ingelheim publication policy. The rights of the investigator and of the sponsor with regard to publication of the results of this trial are described in the investigator contract.