A Study to Evaluate the Safety and Efficacy of an Investigational Drug in HIV Infected Patients (0518-004)(COMPLETED)
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| Study Type: | Interventional |
|---|---|
| Study Design: | Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment |
| Conditions: |
HIV Infections Acquired Immunodeficiency Syndrome |
| Interventions: |
Drug: Comparator: MK0518 monotherapy Drug: Comparator: MK0518 combination therapy Drug: Comparator: efavirenz Drug: Comparator: tenofovir Drug: Comparator: lamivudine Drug: Placebo monotherapy |
Participant Flow
Recruitment Details
| Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations |
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|
Primary therapy period: For Part I (10 day monotherapy): 24-Jan-2005 to 04-May-2005 Part II (Dose Ranging): 14-Jun-2005 to 04-Oct-2006 (48 weeks); 14-Jun-2005 to 12-Jul-2010 (240 weeks) Multicenter (29) in the United States (14) and Ex-US (15) |
Pre-Assignment Details
| Significant events and approaches for the overall study following participant enrollment, but prior to group assignment |
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Patients with Human Immunodeficiency Virus (HIV) Ribonucleic acid (RNA) of at least 5000 copies/mL and cluster of differentiation 4 (CD4) cell counts of at least 100 cells/mm3. All patients must have met laboratory criteria. 206 enrolled; 5 from Cohort I did not continue to the combination phase. Therefore 201 entered the combination phase. |
Reporting Groups
| Description | |
|---|---|
| MK0518 100 mg b.i.d. |
Cohort I-Monotherapy Phase MK0518 100 mg twice daily (b.i.d.) Cohort II Combined-Combination Therapy Phase MK0518 100 mg + tenofovir + lamivudine |
| MK0518 200 mg b.i.d |
Cohort I-Monotherapy Phase MK0518 200 mg b.i.d Cohort II Combined-Combination Therapy Phase MK0518 200 mg + tenofovir + lamivudine |
| MK0518 400 mg b.i.d. |
Cohort I-Monotherapy Phase MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine |
| MK0518 600 mg b.i.d. |
Cohort I-Monotherapy Phase MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine |
| Placebo | Cohort I-Monotherapy Phase Placebo to MK0518 b.i.d. |
| Efavirenz 600 mg q.h.s. | Cohort II Combined-Combination Therapy Phase efavirenz 600 mg every night at bedtime (q.h.s.) |
Participant Flow for 2 periods
Period 1: Cohort I-Monotherapy Phase 10 Days
| MK0518 100 mg b.i.d. | MK0518 200 mg b.i.d | MK0518 400 mg b.i.d. | MK0518 600 mg b.i.d. | Placebo | Efavirenz 600 mg q.h.s. | |
|---|---|---|---|---|---|---|
| STARTED | 7 | 7 | 6 | 8 | 7 | 0 [1] |
| Treated | 7 | 7 | 6 | 8 | 7 | 0 |
| COMPLETED | 7 [2] | 7 [2] | 6 [3] | 8 [3] | 7 [4] | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| [1] | participants only assigned Efavirenz 600 mg q.h.s in Cohort II Combined-Combination Therapy Phase |
|---|---|
| [2] | 7 Subjects Continued to Cohort II Combined-Combination Therapy Phase (48 Weeks) |
| [3] | 6 Subjects Continued to Cohort II Combined-Combination Therapy Phase (48 Weeks) |
| [4] | 4 Subjects Continued to Cohort II, as part of the Efavirenz 600 mg q.d. arm |
Period 2: Cohort I & II-Combination Therapy Phase
| MK0518 100 mg b.i.d. | MK0518 200 mg b.i.d | MK0518 400 mg b.i.d. | MK0518 600 mg b.i.d. | Placebo | Efavirenz 600 mg q.h.s. | |
|---|---|---|---|---|---|---|
| STARTED | 41 [1] | 40 [2] | 41 [3] | 40 [4] | 0 [5] | 39 [6] |
| Treated | 39 | 40 | 41 | 40 | 0 | 38 |
| Never Treated | 2 [7] | 0 | 0 | 0 | 0 | 1 [7] |
| COMPLETED | 27 | 31 | 28 | 30 | 0 | 26 |
| NOT COMPLETED | 14 | 9 | 13 | 10 | 0 | 13 |
| Never Treated | 2 | 0 | 0 | 0 | 0 | 1 |
| Adverse Event | 0 | 1 | 2 | 0 | 0 | 1 |
| Lack of Efficacy | 1 | 3 | 0 | 0 | 0 | 2 |
| Lost to Follow-up | 2 | 1 | 3 | 2 | 0 | 3 |
| Withdrawal by Subject | 1 | 2 | 2 | 5 | 0 | 4 |
| Other Reason | 7 | 1 | 4 | 2 | 0 | 0 |
| Completed Base Study, Did Not Continue | 1 | 1 | 2 | 0 | 0 | 2 |
| Laboratory Adverse Experience | 0 | 0 | 0 | 1 | 0 | 0 |
| [1] | 7 subjects from the Monotherapy Phase and 34 new subjects |
|---|---|
| [2] | 7 subjects from the Monotherapy Phase and 33 new subjects |
| [3] | 6 subjects from the Monotherapy Phase and 35 new subjects |
| [4] | 8 subjects from the Monotherapy Phase and 32 new subjects |
| [5] | participants only assigned Placebo in Cohort I-Monotherapy Phase. |
| [6] | 4 subjects from the Monotherapy Phase (Placebo)and 35 new subjects |
| [7] | Randomised in Cohort II did not start Period |
Baseline Characteristics
Reporting Groups
| Description | |
|---|---|
| MK0518 100 mg b.i.d. |
Cohort I-Monotherapy Phase (10 Days) MK0518 100 mg twice daily (b.i.d.) Cohort II Combined-Combination Therapy Phase (48 Weeks) MK0518 100 mg b.i.d |
| MK0518 200 mg b.i.d |
Cohort I-Monotherapy Phase (10 Days) MK0518 200 mg b.i.d Cohort II Combined-Combination Therapy Phase (48 Weeks) MK0518 200 mg + tenofovir + lamivudine |
| MK0518 400 mg b.i.d. |
Cohort I-Monotherapy Phase (10 Days) MK0518 400 mg b.i.d. Cohort II Combined-Combination Therapy Phase (48 Weeks) MK0518 400 mg + tenofovir + lamivudine |
| MK0518 600 mg b.i.d. |
Cohort I-Monotherapy Phase (10 Days) MK0518 600 mg b.i.d. Cohort II Combined-Combination Therapy Phase (48 Weeks) MK0518 600 mg + tenofovir + lamivudine |
| Placebo / Efavirenz 600 mg Once Daily (q.d.) |
Cohort I-Monotherapy Phase (10 Days) Placebo to MK0518 b.i.d. Cohort II Combined-Combination Therapy Phase (48 Weeks) Efavirenz + Tenofovir + Lamivudine |
| Total | Total of all reporting groups |
Baseline Measures
| MK0518 100 mg b.i.d. | MK0518 200 mg b.i.d | MK0518 400 mg b.i.d. | MK0518 600 mg b.i.d. | Placebo / Efavirenz 600 mg Once Daily (q.d.) | Total | |
|---|---|---|---|---|---|---|
|
Number of Participants
[units: participants] |
41 | 40 | 41 | 42 | 42 | 206 |
|
Age
[1] [units: Years] Mean ( Full Range ) |
||||||
| Cohort I |
46
( 31 to 68 ) |
37
( 22 to 57 ) |
41
( 25 to 55 ) |
39
( 30 to 49 ) |
36
( 21 to 51 ) |
40
( 21 to 68 ) |
| Cohort II |
34
( 19 to 58 ) |
31
( 21 to 56 ) |
34
( 19 to 50 ) |
36
( 20 to 49 ) |
36
( 22 to 54 ) |
35
( 19 to 58 ) |
| Cohort I & II Combined |
37
( 19 to 68 ) |
34
( 21 to 57 ) |
36
( 19 to 55 ) |
37
( 20 to 49 ) |
36
( 22 to 54 ) |
36
( 19 to 68 ) |
|
Gender, Customized
[units: participants] |
||||||
| Female (Cohort I) | 0 | 1 | 0 | 0 | 1 | 2 |
| Male (Cohort I) | 7 | 6 | 6 | 8 | 6 | 33 |
| Female (Cohort II) | 6 | 10 | 4 | 11 | 8 | 39 |
| Male (Cohort II) | 27 | 23 | 31 | 23 | 26 | 130 |
| Never Treated Cohort II | 1 | 0 | 0 | 0 | 1 | 2 |
|
Race/Ethnicity, Customized
[units: participants] |
||||||
| White (Cohort I) | 4 | 4 | 3 | 8 | 3 | 22 |
| Black (Cohort I) | 1 | 1 | 0 | 0 | 0 | 2 |
| Asian (Cohort I) | 0 | 0 | 0 | 0 | 1 | 1 |
| Hispanic (Cohort I) | 2 | 2 | 3 | 0 | 3 | 10 |
| White (Cohort II) | 4 | 10 | 11 | 8 | 10 | 43 |
| Black (Cohort II) | 1 | 1 | 1 | 0 | 0 | 3 |
| Asian (Cohort II) | 3 | 6 | 8 | 7 | 8 | 32 |
| Hispanic (Cohort II) | 12 | 9 | 10 | 9 | 10 | 50 |
| Other (Cohort II) | 13 | 7 | 5 | 10 | 6 | 41 |
| Never Treated (Cohort II) | 1 | 0 | 0 | 0 | 1 | 2 |
|
Cluster of differentiation 4 (CD4) Cell Count
[1] [units: cells/mm^3] Mean ( Full Range ) |
||||||
| Cohort I |
415
( 138 to 745 ) |
343
( 149 to 624 ) |
256
( 96 to 602 ) |
569
( 241 to 1034 ) |
343
( 115 to 599 ) |
394
( 96 to 1034 ) |
| Cohort II |
293
( 76 to 736 ) |
292
( 70 to 723 ) |
348
( 95 to 1017 ) |
245
( 99 to 734 ) |
276
( 77 to 744 ) |
291
( 70 to 1017 ) |
| Cohort I and II Combined |
272
( 76 to 758 ) |
277
( 70 to 723 ) |
293
( 95 to 1017 ) |
244
( 99 to 786 ) |
225
( 77 to 744 ) |
266
( 70 to 1017 ) |
|
Plasma Human Immunodeficiency Virus (HIV) Ribonucleic acid (RNA)
[1] [units: copies/mL] Geometric Mean ( Full Range ) |
||||||
| Cohort I |
44989
( 3890 to 225000 ) |
34143
( 5420 to 168000 ) |
37728
( 6850 to 152000 ) |
93911
( 17100 to 388000 ) |
58412
( 7630 to 456000 ) |
51496
( 3890 to 456000 ) |
| Cohort II |
65982
( 4200 to 750000 ) |
73646
( 7490 to 750000 ) |
47019
( 2440 to 499000 ) |
61929
( 3450 to 750000 ) |
76752
( 7500 to 675000 ) |
63965
( 2440 to 750000 ) |
| Cohort I and II Combined |
58206
( 4200 to 750000 ) |
64715
( 7490 to 750000 ) |
43083
( 2440 to 499000 ) |
57919
( 3450 to 750000 ) |
67554
( 3340 to 675000 ) |
57437
( 2440 to 750000 ) |
| [1] | Cohort I Participants: MK0518 100 mg b.i.d. (7); MK0518 200 mg b.i.d. (7); MK0518 400 mg b.i.d. (6); MK0518 600 mg b.i.d. (8); Placebo Cohort (7) Cohort II Participants: MK0518 100 mg b.i.d. (33); MK0518 200 mg b.i.d. (33); MK0518 400 mg b.i.d. (35); MK0518 600 mg b.i.d. (34); Efavirenz 600 mg q.d. (34) Cohort I & II Participants Combined: MK0518 100 mg b.i.d. (39); MK0518 200 mg b.i.d. (40); MK0518 400 mg b.i.d. (41); MK0518 600 mg b.i.d. (40); Efavirenz 600 mg q.d. (38) |
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Outcome Measures
| 1. Primary: | Change From Baseline in Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) on Day 10 (Cohort I) [ Time Frame: Baseline and Day 10 ] |
| 2. Primary: | Number of Patients With Clinical Adverse Experiences (CAEs) and Number of Patients With Serious CAEs at Day 10 (Cohort I) [ Time Frame: 10 days ] |
| 3. Primary: | Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 24 (Cohort II) [ Time Frame: Week 24 ] |
| 4. Primary: | Number of Patients With Clinical Adverse Experiences (CAEs) [ Time Frame: 48 weeks ] |
| 5. Primary: | Number of Patients With Serious CAEs (Cohort I and II Combined) [ Time Frame: 48 weeks ] |
| 6. Primary: | Number of Patients With Serious CAEs and Non-serious CAEs at Week 144 [ Time Frame: 144 Weeks ] |
| 7. Primary: | Number of Participants With Clinical Adverse Experiences (AEs)and Serious Adverse Experiences (SAEs) [ Time Frame: Week 240 ] |
| 8. Primary: | Number of Participants With HIV RNA (Human Immunodeficiency Virus Ribonucleic Acid) Levels Below 50 Copies/mL at Week 240 [ Time Frame: Week 240 ] |
| 9. Secondary: | Number of Participants With HIV RNA Levels Below 50 Copies/mL at Week 24 (Cohort II) [ Time Frame: Week 24 ] |
| 10. Secondary: | Change From Baseline in Plasma HIV RNA at Week 24 (Cohort II) [ Time Frame: Baseline and Week 24 ] |
| 11. Secondary: | Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 24 (Cohort II) [ Time Frame: Baseline and Week 24 ] |
| 12. Secondary: | Number of Patients With HIV RNA Level Below 50 Copies/mL and HIV RNA Level Below 400 Copies/mL at Week 96 [ Time Frame: 96 Weeks ] |
| 13. Secondary: | Change From Baseline in Plasma HIV RNA at Week 96 [ Time Frame: Baseline and Week 96 ] |
| 14. Secondary: | Change From Baseline in CD4 Cell Count at Week 96 [ Time Frame: Baseline and Week 96 ] |
| 15. Secondary: | Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 240 [ Time Frame: Week 240 ] |
| 16. Secondary: | Change From Baseline in Plasma HIV RNA at Week 240 [ Time Frame: Baseline and Week 240 ] |
| 17. Secondary: | Change From Baseline in CD4 (T-helper) Cell Count at Week 240 [ Time Frame: Baseline and Week 240 ] |
| 18. Other Pre-specified: | Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 48 [ Time Frame: 48 weeks ] |
| 19. Other Pre-specified: | Number of Patients With Drug-related CAEs [ Time Frame: 48 weeks ] |
| 20. Other Pre-specified: | Number of Patients With Serious Drug-related CAEs [ Time Frame: 48 Weeks ] |
| 21. Other Pre-specified: | Number of Patients That Discontinued With CAEs [ Time Frame: 48 Weeks ] |
| 22. Other Pre-specified: | Number of Patients With Laboratory Adverse Experiences (LAEs) [ Time Frame: 48 Weeks ] |
| 23. Other Pre-specified: | Number of Patients With Serious LAEs [ Time Frame: 48 Weeks ] |
| 24. Other Pre-specified: | Number of Patients With Drug-related LAEs [ Time Frame: 48 Weeks ] |
| 25. Other Pre-specified: | Number of Patients With Serious Drug-related LAEs [ Time Frame: 48 Weeks ] |
| 26. Other Pre-specified: | Number of Patients That Discontinued With LAEs [ Time Frame: 48 Weeks ] |