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: October 23, 2013
Last verified: October 2013
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
  Hide Participant Flow

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)


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.


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)




  Outcome Measures
  Show All 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 ]
  Hide Outcome Measure 22

Measure Type Other Pre-specified
Measure Title Number of Patients With Laboratory Adverse Experiences (LAEs)
Measure Description A laboratory adverse experience (LAE) is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the SPONSOR'S product, whether or not considered related to the use of the product
Time Frame 48 Weeks  
Safety Issue Yes  

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 All

Patients As Treated (APaT) approach.


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

EFV Combo Therapy

EFV Combo Therapy Phase - Cohort II

efavirenz 600 mg daily at bedtime (qhs) + tenofovir + lamivudine

This arm included participants from Cohort I who were randomized to placebo.


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]
  39     40     41     40     38  
Number of Patients With Laboratory Adverse Experiences (LAEs)  
[units: participants]
         
With LAEs     8     7     11     5     8  
Without LAEs     31     33     30     35     30  

No statistical analysis provided for Number of Patients With Laboratory Adverse Experiences (LAEs)



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 ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
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
No text entered.  


Results Point of Contact:  
Name/Title: Vice President, Late Stage Development Group Leader
Organization: Merck Sharp & Dohme Corp
phone: 1-800-672-6372
e-mail: ClinicalTrialsDisclosure@merck.com


Publications:


Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00100048     History of Changes
Other Study ID Numbers: 0518-004, 2004_096
Study First Received: December 22, 2004
Results First Received: January 21, 2010
Last Updated: October 23, 2013
Health Authority: United States: Food and Drug Administration