Safety and Efficacy of an Investigational Drug in Human Immunodeficiency Virus (HIV)-Infected Patients Failing Current Antiretroviral Therapies (0518-005)(COMPLETED)

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Primary therapy period: 22-Apr-2005 to 09-Nov-2006 Multicenter (31) in the United States (15) and outside the United States (16)

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients failed prior antiretroviral therapy (HIV RNA >5000 copies/mL), and had documented resistance to at least one drug in each class of licensed oral antiretroviral therapy (Nucleoside Reverse Transcriptase inhibitors, Non-Nucleoside Reverse Transcriptase inhibitors and Protease Inhibitors). All patients must have met laboratory criteria.

Reporting Groups

	Description
MK0518 200 mg b.i.d.	Optimized background antiretroviral therapy (OBT), if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 200 mg twice a day (b.i.d.). Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.
MK0518 400 mg b.i.d.	OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 400 mg b.i.d.
MK0518 600 mg b.i.d.	OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 600 mg b.i.d.. Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.
Placebo	OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 matching placebo b.i.d.. Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.

Participant Flow for 3 periods

Period 1:   Double-Blind (DB)

	MK0518 200 mg b.i.d.	MK0518 400 mg b.i.d.	MK0518 600 mg b.i.d.	Placebo
STARTED	44	45	45	45
Treated	43	45	45	45
COMPLETED	30	31	33	6
NOT COMPLETED	14	14	12	39
Never Treated	1	0	0	0
Adverse Event	2	0	1	1
Lack of Efficacy	11	14	11	38

Period 2:   Open-Label Continuation of DB

	MK0518 200 mg b.i.d.	MK0518 400 mg b.i.d.	MK0518 600 mg b.i.d.	Placebo
STARTED	30	31	33	6
COMPLETED	23	21	24	5
NOT COMPLETED	7	10	9	1
Adverse Event	3	1	0	0
Lack of Efficacy	1	4	3	1
Lost to Follow-up	1	1	1	0
Withdrawal by Subject	0	1	3	0
Patient did not continue in extension	1	0	0	0
Patient moved/site stopped trial	1	3	2	0

Period 3:   Open-Label Post Virologic Failure(OLPVF)

	MK0518 200 mg b.i.d.	MK0518 400 mg b.i.d.	MK0518 600 mg b.i.d.	Placebo
STARTED	11 [1]	13 [1]	11 [1]	37 [1]
COMPLETED	2	7	5	19
NOT COMPLETED	9	6	6	18
Adverse Event	0	0	0	1
Lack of Efficacy	7	6	5	10
Lost to Follow-up	1	0	0	1
Withdrawal by Subject	0	0	0	5
Patient moved/Site stopped trial	1	0	1	1

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
MK0518 200 mg b.i.d.	Optimized background antiretroviral therapy (OBT), if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 200 mg twice a day (b.i.d.). Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.
MK0518 400 mg b.i.d.	OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 400 mg b.i.d.
MK0518 600 mg b.i.d.	OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 600 mg b.i.d.. Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.
Placebo	OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 matching placebo b.i.d.. Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.
Total	Total of all reporting groups

Baseline Measures

	MK0518 200 mg b.i.d.	MK0518 400 mg b.i.d.	MK0518 600 mg b.i.d.	Placebo	Total
Number of Participants   [units: participants]	43	45	45	45	178
Age   [units: years] Mean ( Full Range )	44.0     ( 18 to 57 )	45.1     ( 32 to 69 )	43.8     ( 25 to 63 )	43.3     ( 29 to 59 )	44.1     ( 18 to 69 )
Gender   [units: participants]
Female	7	5	4	5	21
Male	36	40	41	40	157
Race/Ethnicity, Customized   [units: participants]
White	36	35	32	33	136
Black	3	5	7	5	20
Asian	0	0	2	1	3
Hispanic	4	5	4	5	18
Others	0	0	0	1	1
Cluster of Differentiation 4 (CD4) Cell Count   [units: Cells/mm3] Mean ( Full Range )	244.9     ( 30 to 1153 )	220.6     ( 68 to 673 )	220.4     ( 30 to 663 )	274.0     ( 37 to 880 )	239.9     ( 30 to 1153 )
Plasma HIV RNA   [units: log10 copies/mL] Mean ( Full Range )	4.6     ( 3.5 to 5.9 )	4.8     ( 3.7 to 5.9 )	4.7     ( 3.8 to 5.8 )	4.7     ( 3.6 to 5.8 )	4.7     ( 3.5 to 5.9 )
Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA)   [units: Copies/mL] Mean ( Full Range )	44642.6     ( 3000 to 750000 )	59107.9     ( 4770 to 750000 )	49064.8     ( 7030 to 589000 )	47432.6     ( 3630 to 611000 )	49841.6     ( 3000 to 750000 )

1.  Primary:

Change From Baseline in Plasma HIV RNA (log10 Copies/mL) at Week 24   [ Time Frame: Baseline and Week 24 ]

2.  Secondary:

Number of Patients With Virologic Responses at Week 24   [ Time Frame: 24 weeks ]

3.  Secondary:

Change From Baseline in CD4 Cell Count at Week 24   [ Time Frame: Baseline and Week 24 ]

4.  Secondary:

Number of Patients With Clinical Adverse Experiences (CAEs) at 48 Weeks   [ Time Frame: 48 weeks ]

5.  Secondary:

Number of Patients With Serious CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

6.  Secondary:

Number of Patients With Drug-related CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

7.  Secondary:

Number of Patients With Serious Drug-related CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

8.  Secondary:

Number of Patients That Died by 48 Weeks   [ Time Frame: 48 weeks ]

9.  Secondary:

Number of Patients That Discontinued With CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

10.  Secondary:

Number of Patients That Discontinued With Drug-related CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

11.  Secondary:

Number of Patients That Discontinued With Serious CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

12.  Secondary:

Number of Patients That Discontinued With Serious Drug-related CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

13.  Secondary:

Number of Patients With Laboratory Adverse Experiences (LAEs) at 48 Weeks   [ Time Frame: 48 weeks ]

14.  Secondary:

Number of Patients With Drug-related LAEs at 48 Weeks   [ Time Frame: 48 weeks ]

15.  Secondary:

Number of Patients Discontinued With Laboratory Adverse Experiences (LAEs) at 48 Weeks   [ Time Frame: 48 weeks ]

16.  Secondary:

Number of Patients Discontinued With Drug-related LAEs at 48 Weeks   [ Time Frame: 48 weeks ]

17.  Secondary:

Number of Patients With Clinical Adverse Experiences (CAEs) at 96 Weeks   [ Time Frame: 96 weeks ]

18.  Secondary:

Number of Patients With Serious CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

19.  Secondary:

Number of Patients With Drug-related CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

20.  Secondary:

Number of Patients With Serious Drug-related CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

21.  Secondary:

Number of Patients That Died by 96 Weeks   [ Time Frame: 96 weeks ]

22.  Secondary:

Number of Patients That Discontinued With CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

23.  Secondary:

Number of Patients That Discontinued With Drug-related CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

24.  Secondary:

Number of Patients That Discontinued With Serious CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

25.  Secondary:

Number of Patients That Discontinued With Serious Drug-related CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

26.  Secondary:

Number of Patients With Laboratory Adverse Experiences (LAEs) at 96 Weeks   [ Time Frame: 96 weeks ]

27.  Secondary:

Number of Patients With Drug-related LAEs at 96 Weeks   [ Time Frame: 96 weeks ]

28.  Secondary:

Number of Patients Discontinued With Laboratory Adverse Experiences (LAEs) at 96 Weeks   [ Time Frame: 96 weeks ]

29.  Secondary:

Number of Patients Discontinued With Drug-related LAEs at 96 Weeks   [ Time Frame: 96 weeks ]

30.  Secondary:

Number of Patients With Clinical Adverse Experiences (CAEs) at 168 Weeks   [ Time Frame: 168 weeks ]

31.  Secondary:

Number of Patients With Serious CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

32.  Secondary:

Number of Patients With Drug-related CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

33.  Secondary:

Number of Patients With Serious Drug-related CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

34.  Secondary:

Number of Patients That Died by 168 Weeks   [ Time Frame: 168 weeks ]

35.  Secondary:

Number of Patients That Discontinued With CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

36.  Secondary:

Number of Patients That Discontinued With Drug-related CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

37.  Secondary:

Number of Patients That Discontinued With Serious CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

38.  Secondary:

Number of Patients That Discontinued With Serious Drug-related CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

39.  Secondary:

Number of Patients With Laboratory Adverse Experiences (LAEs) at 168 Weeks   [ Time Frame: 168 weeks ]

40.  Secondary:

Number of Patients With Serious LAEs at 168 Weeks   [ Time Frame: 168 weeks ]

41.  Secondary:

Number of Patients Discontinued With Drug-related LAEs at 168 Weeks   [ Time Frame: 168 weeks ]

42.  Secondary:

Number of Patients With Drug-related LAEs at 168 Weeks   [ Time Frame: 168 weeks ]

43.  Secondary:

Number of Patients With Serious Drug-related LAEs at 168 Weeks   [ Time Frame: 168 weeks ]

44.  Secondary:

Number of Patients Discontinued With LAEs at 168 Weeks   [ Time Frame: 168 weeks ]

45.  Post-Hoc:

Number of Patients With Virologic Responses at Week 168 in Combined Substudies   [ Time Frame: 168 weeks ]

46.  Other Pre-specified:

Change From Baseline in Plasma HIV RNA (log10 Copies/mL) at Week 168 in Combined Substudies   [ Time Frame: Baseline and Week 168 ]

47.  Other Pre-specified:

Change From Baseline in CD4 Cell Count at Week 168 in Combined Substudies   [ Time Frame: Baseline and Week 168 ]

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Due to a 3:1 randomization of MK-0518 to placebo and more discontinuations for placebo in the doubleblind phase, exposure for MK-0518 and placebo differs significantly with follow-up times of 336.3 and 39.7 patient-years, respectively.