A Study to Evaluate the Safety and Efficacy of an Investigational Drug in HIV Infected Patients (0518-004)(COMPLETED)

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Merck Sharp & Dohme Corp.

ClinicalTrials.gov Identifier:

NCT00100048

First received: December 22, 2004

Last updated: September 26, 2014

Last verified: September 2014

History of Changes

Results First Received: January 21, 2010

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

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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: 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)

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

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
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.

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

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

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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 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)

[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)

Outcome Measures

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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 ]

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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 ]

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3. Primary:

Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 24 (Cohort II) [ Time Frame: Week 24 ]

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4. Primary:

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

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5. Primary:

Number of Patients With Serious CAEs (Cohort I and II Combined) [ Time Frame: 48 weeks ]

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6. Primary:

Number of Patients With Serious CAEs and Non-serious CAEs at Week 144 [ Time Frame: 144 Weeks ]

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7. Primary:

Number of Participants With Clinical Adverse Experiences (AEs)and Serious Adverse Experiences (SAEs) [ Time Frame: Week 240 ]

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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 ]

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9. Secondary:

Number of Participants With HIV RNA Levels Below 50 Copies/mL at Week 24 (Cohort II) [ Time Frame: Week 24 ]

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Measure Type	Secondary
Measure Title	Number of Participants With HIV RNA Levels Below 50 Copies/mL at Week 24 (Cohort II)
Measure Description	No text entered.
Time Frame	Week 24
Safety Issue	No

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.
The analysis population is based upon the modified intent to treat (MITT) approach, where patients are included in the treatment group to which they were randomized. Patients who were randomized but never dosed are not included in the analysis.

Reporting Groups

	Description
MK0518 100 mg b.i.d.	Cohort II Combined-Combination Therapy Phase MK0518 100 mg + tenofovir + lamivudine
MK0518 200 mg b.i.d	Cohort II Combined-Combination Therapy Phase MK0518 200 mg + tenofovir + lamivudine
MK0518 400 mg b.i.d.	Cohort II Combined-Combination Therapy Phase MK0518 400 mg + tenofovir + lamivudine
MK0518 600 mg b.i.d.	Cohort II Combined-Combination Therapy Phase MK0518 600 mg + tenofovir + lamivudine
EFV Combo Therapy	EFV Combo Therapy Phase - Cohort II efavirenz + tenofovir + lamivudine

Measured Values

	MK0518 100 mg b.i.d.	MK0518 200 mg b.i.d	MK0518 400 mg b.i.d.	MK0518 600 mg b.i.d.	EFV Combo Therapy
Number of Participants Analyzed [units: participants]	33	33	35	34	34
Number of Participants With HIV RNA Levels Below 50 Copies/mL at Week 24 (Cohort II) [units: participants]	28	27	33	32	31

No statistical analysis provided for Number of Participants With HIV RNA Levels Below 50 Copies/mL at Week 24 (Cohort II)

10. Secondary:

Change From Baseline in Plasma HIV RNA at Week 24 (Cohort II) [ Time Frame: Baseline and Week 24 ]

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11. Secondary:

Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count at Week 24 (Cohort II) [ Time Frame: Baseline and Week 24 ]

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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 ]

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13. Secondary:

Change From Baseline in Plasma HIV RNA at Week 96 [ Time Frame: Baseline and Week 96 ]

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14. Secondary:

Change From Baseline in CD4 Cell Count at Week 96 [ Time Frame: Baseline and Week 96 ]

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15. Secondary:

Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 240 [ Time Frame: Week 240 ]

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16. Secondary:

Change From Baseline in Plasma HIV RNA at Week 240 [ Time Frame: Baseline and Week 240 ]

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17. Secondary:

Change From Baseline in CD4 (T-helper) Cell Count at Week 240 [ Time Frame: Baseline and Week 240 ]

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18. Other Pre-specified:

Number of Participants With HIV RNA Levels Below 400 Copies/mL at Week 48 [ Time Frame: 48 weeks ]

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19. Other Pre-specified:

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

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20. Other Pre-specified:

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

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21. Other Pre-specified:

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

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22. Other Pre-specified:

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

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23. Other Pre-specified:

Number of Patients With Serious LAEs [ Time Frame: 48 Weeks ]

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24. Other Pre-specified:

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

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25. Other Pre-specified:

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

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26. Other Pre-specified:

Number of Patients That Discontinued With LAEs [ Time Frame: 48 Weeks ]

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Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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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
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