A Study to Compare Effectiveness and Safety of Darunavir/Ritonavir (DRV/Rtv) 800mg/100mg Once Daily Versus DRV/Rtv 600mg/100mg Twice Daily in Early Treatment-Experienced HIV-1 Infected Patients (ODIN)

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Tibotec Pharmaceuticals, Ireland

ClinicalTrials.gov Identifier:

NCT00524368

First received: August 30, 2007

Last updated: February 12, 2013

Last verified: February 2013

History of Changes

Results First Received: August 27, 2010

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Human Immunodeficiency Virus - Type 1
Interventions:	Drug: Darunavir (DRV) Drug: Ritonavir (rtv)

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
One hundred thirteen investigators in 21 countries participated in this study.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
In total 1092 participants were screened, of which 590 participants were randomly assigned and treated (294 participants were treated with DRV/rtv 800/100 mg once daily, and 296 participants with DRV/rtv 600/100 mg twice daily.

Reporting Groups

	Description
DRV/Rtv 800/100 mg Once Daily	Two 400 mg tablets of darunavir (DRV) + one 100 mg capsule of ritonavir (rtv) once daily
DRV/Rtv 600/100 mg Twice Daily	One 600 mg darunavir (DRV) tablet + one 100 mg capsule of ritonavir (rtv) given twice daily

Participant Flow: Overall Study

	DRV/Rtv 800/100 mg Once Daily	DRV/Rtv 600/100 mg Twice Daily
STARTED	294	296
COMPLETED	253	248
NOT COMPLETED	41	48
Adverse Event	10	12
Lost to Follow-up	9	13
Withdrawal by Subject	4	5
Non-compliant	8	9
Reached a Virologic Endpoint	3	2
Sponsor's Decision	2	0
Ineligible to Continue the study	2	5
Unspecified	3	2

Baseline Characteristics

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Reporting Groups

	Description
DRV/Rtv 800/100 mg Once Daily	Two 400 mg tablets of darunavir (DRV) + one 100 mg capsule of ritonavir (rtv) once daily
DRV/Rtv 600/100 mg Twice Daily	One 600 mg darunavir (DRV) tablet + one 100 mg capsule of ritonavir (rtv) given twice daily
Total	Total of all reporting groups

Baseline Measures

	DRV/Rtv 800/100 mg Once Daily	DRV/Rtv 600/100 mg Twice Daily	Total
Number of Participants [units: participants]	294	296	590
Age [units: years] Mean ± Standard Deviation	40.2 ± 9.09	40.7 ± 9.50	40.5 ± 9.29
Gender [units: participants]
Female	115	98	213
Male	179	198	377
Age (years) (categorical) [units: participants]
Age <= 30	35	35	70
30 < Age <= 45	180	169	349
45 < Age <= 55	64	72	136
55 < Age <= 65	14	18	32
Age > 65	1	2	3
Hepatitis B or C Co-infection Status [units: participants]
Negative	267	255	522
Positive	25	37	62
Unknown	2	4	6

Outcome Measures

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1. Primary:

Virological Response at Week 48 (Number of Participants With Plasma Viral Load Less Than 50 Copies/mL) - as Defined by the Time to Loss of Virologic Response (TLOVR) Algorithm [ Time Frame: 48 Weeks ]

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2. Secondary:

Virologic Response at Week 48 (Viral Load Less Than 400 Copies/mL) [ Time Frame: 48 weeks ]

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3. Secondary:

Change in log10 Viral Load From Baseline at Week 48 [ Time Frame: 48 weeks ]

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4. Secondary:

Time to Reach First Virologic Response [ Time Frame: 48 weeks ]

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5. Secondary:

Time to Loss of Virologic Response [ Time Frame: 48 weeks ]

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6. Secondary:

Time-averaged Difference (DAVG) of log10 Plasma Viral Load Over 48 Weeks [ Time Frame: 48 weeks ]

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7. Secondary:

Change in CD4+ Cell Count From Baseline [ Time Frame: 48 Weeks ]

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8. Secondary:

Change From Baseline in Total Functional Assessment of HIV Infection (FAHI) Score [ Time Frame: 48 weeks ]

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Measure Type	Secondary
Measure Title	Change From Baseline in Total Functional Assessment of HIV Infection (FAHI) Score
Measure Description	The FAHI is a 44-item questionnaire and incorporates 5 functional scales (physical well-being, emotional well-being/living with HIV, functional and global well-being, social well-being, and cognitive functioning). Each scale included several questions (all 5 scales include total 44 questions). For each question, participants gave a score of either 0 (not at all), 1 (a little bit), 2 (somewhat), 3 (quite a bit) and 4 (very much). Total FAHI imputed score is calculated by adding scores for each question. The range of total FAHI score is 0 to 176. Higher scores indicate worsening.
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.
Intention To Treat (ITT) population - last observation carried forward (LOCF): Intermittent missing values and missing values due to premature discontinuation were imputed with the last observation.

Reporting Groups

	Description
DRV/Rtv 800/100 mg Once Daily	Two 400 mg tablets of darunavir (DRV) + one 100 mg capsule of ritonavir (rtv) once daily
DRV/Rtv 600/100 mg Twice Daily	One 600 mg darunavir (DRV) tablet + one 100 mg capsule of ritonavir (rtv) given twice daily

Measured Values

	DRV/Rtv 800/100 mg Once Daily	DRV/Rtv 600/100 mg Twice Daily
Number of Participants Analyzed [units: participants]	294	296
Change From Baseline in Total Functional Assessment of HIV Infection (FAHI) Score [units: Scores on a scale] Median ( Full Range )
FAHI score at baseline	129 ( 31 to 175 )	123.5 ( 33 to 174 )
Change from baseline in FAHI score at Week 48	2.5 ( -74 to 81 )	0.0 ( -75 to 81 )

Statistical Analysis 1 for Change From Baseline in Total Functional Assessment of HIV Infection (FAHI) Score

Groups ^[1]	All groups
Method ^[2]	ANCOVA
P Value ^[3]	0.761
Difference in least square means ^[4]	0.55
Standard Error of the mean	± 1.79
95% Confidence Interval	( -2.97 to 4.06 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	Including factors for treatment, and baseline log10 plasma viral load and baseline FAHI score as covariates
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	Difference in least square means DRV/rtv once daily minus DRV/rtv twice daily estimated from the ANCOVA model.

9. Secondary:

Percentage of Participants Adherent/Non-adherent to ARV as Determined by Modified Medication Adherence Self Report Inventory (M-MASRI) Questionnaire at Week 48 [ Time Frame: 48 weeks ]

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10. Secondary:

Area Under the Curve From the Time of Study Medication Administration Upto 24 Hour Postdose (AUC24h) of DRV and Rtv [ Time Frame: 0 hour predose and 1 hour post dose measured at Weeks 4 and 24. Any time point measured at Weeks 8 and 48. ]

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11. Secondary:

Predose Plasma Concentration (C0h) of DRV and Rtv. [ Time Frame: 0 hour predose and 1 hour post dose measured at Weeks 4 and 24. Any time point measured at Weeks 8 and 48 ]

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12. Secondary:

Number of Participants Developing Mutations at Endpoint [ Time Frame: 48 weeks ]

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Serious Adverse Events

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The Sponsor will not unreasonably withhold consent to publish the data generated in this trial. However, it is the policy of the Sponsor not to allow the investigators to publish their results or findings prior to the Sponsor’s publication of the overall trial results. The investigator agrees that before he/she publishes any results of this trial, he/she shall allow at least 45 days for the Sponsor to review the prepublication manuscript prior to submission of the manuscript to the publisher.

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: Medical Leader
Organization: Tibotec Pharmaceuticals, Ireland
phone: +32 015 461 497

No publications provided

Responsible Party:	Tibotec Pharmaceuticals, Ireland
ClinicalTrials.gov Identifier:	NCT00524368 History of Changes
Obsolete Identifiers:	NCT00613990
Other Study ID Numbers:	CR013783, TMC114-TiDP31-C229, 2007-001939-61
Study First Received:	August 30, 2007
Results First Received:	August 27, 2010
Last Updated:	February 12, 2013
Health Authority:	United States: Food and Drug Administration Great Britain: Research Ethics Committee

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