Human Immunodeficiency Virus (HIV) Postexposure Prophylaxis (PEP) With Darunavir/Ritonavir (DRV/r) (PEPDar)

Study Description

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Brief Summary:

The primary purpose of this study is to assess the rate of early discontinuation from randomized Human Immunodeficiency Virus (HIV) Postexposure Prophylaxis (PEP) for any reason other than confirmation of the negative HIV infection status of the index person in patients receiving HIV PEP for at least 28 and a maximum of 30 days.

Condition or disease	Intervention/treatment	Phase
Human Immunodeficiency Virus (HIV)	Drug: Darunavir/Ritonavir (DRV/r); Drug: Lopinavir in fixed combination with Ritonavir; Drug: Zidovudine; Drug: NRTIs; Drug: Efavirenz	Phase 3

Detailed Description:

This is a randomized (study medication assigned by chance), open-label (all people involved know the identity of the intervention), active-controlled (patients are assigned to either a recognized effective treatment or the study medication), parallel-group (each treatment group will be treated at the same time), multicenter study comparing DRV/r PEP (DRV/r administered with 2 NRTIs selected at the discretion of the investigator) to standard of care PEP (as per German-Austrian guidelines) in patients at risk of HIV infection due to HIV exposure through occupational injury and non-occupational exposure. This study consists of screening period, treatment period and a follow up period. HIV PEP will be administered for a total of at least 28 days and maximum of 30 days during treatment period, including any prestudy HIV PEP initiated before screening. Approximately 318 patients will be screened and enrolled to ensure that at least 131 patients are randomly assigned to receive DRV/r PEP or standard of care PEP. Safety will be evaluated during the entire study period. Data relating to a patient's functional impairment in conjunction with HIV PEP will be collected on Day 1 as baseline data, and further on Days 14 and 28 as well as at Month 3.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	312 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	HIV Postexposure Prophylaxis With Darunavir/r (PEPDar)
Actual Study Start Date :	November 25, 2011
Actual Primary Completion Date :	August 1, 2013
Actual Study Completion Date :	September 28, 2013

Arms and Interventions

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Arm	Intervention/treatment
Experimental: DRV/r with 2 NRTIs; DRV/r 800/100 mg q.d. with 2 NRTIs: darunavir (800 mg) in combination with low-dose ritonavir (100 mg) administered once a day for at least 28 days and a maximum of 30 days along with 2 nucleoside/nucleotide analogue reverse transcriptase inhibitors (NRTIs).	Drug: Darunavir/Ritonavir (DRV/r); Darunavir (DRV) type=exact number, unit=mg, number=800, form=tablet, route=oral use. Tablet is taken once a day, for 28 days; Ritonavir (r) type=exact number, unit=mg, number=100, form=tablet, route=oral use. Tablet is taken once a day, for at least 28 days and a maximum of 30 days.; Drug: NRTIs; The NRTIs (including tenofovir/emtricitabine [Truvada], lamivudine/zidovudine [Combivir]) will be administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.
Active Comparator: Comparator standard of care HIV PEP; Comparator standard of care HIV PEP (as per German-Austrian Guidelines): Administration of the standard of care HIV PEP (postexposure prophylaxis) consisting of 2 NRTIs plus third partner.	Drug: Lopinavir in fixed combination with Ritonavir; type=exact number, unit=mg, number=400/100, form=tablet, route=oral use. Tablet is taken once or twice a day, for at least 28 days and a maximum of 30 days.; Other Name: Kaletra; Drug: Zidovudine; type=exact number, unit=mg, number=250, form=tablet, route=oral use. Tablet is taken twice a day, for at least 28 days and a maximum of 30 days.; Other Name: Retrovir; Drug: NRTIs; The NRTIs (including tenofovir/emtricitabine [Truvada], lamivudine/zidovudine [Combivir]) will be administered as per the individual Summary of Product Characteristics (SmPCs) at the discretion of either the treating physician or Investigator.; Drug: Efavirenz; type=exact number, unit=mg, number=600, form=tablet, route=oral use. Tablet is taken once a day, for at least 28 days and a maximum of 30 days.; Other Name: Sustiva

Outcome Measures

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Primary Outcome Measures :

1. Number of Participants With Early Discontinuation From Randomized Human Immunodeficiency Virus Postexposure Prophylaxis (HIV PEP) [ Time Frame: Up to 30 days ]
   Number of participants with early discontinuation from randomized HIV PEP for any reason other than confirmation of the negative HIV infection status of the index person in participants receiving HIV PEP for at least 28 days and a maximum of 30 days was assessed. Per protocol (PP) population included all participants in modified intention-to-treat (mITT [defined as all participants who were assigned to receive randomized HIV PEP and were not discontinued due to confirmation of the negative HIV infection status of the index person]) excluding participants with: No indication for HIV PEP; Initiation of PEP >72 hours after injury; Discontinuation of HIV PEP due to confirmation of HIV negative status of index person and if index person bears resistant virus against HIV PEP components prescribed; incorrect HIV PEP; no intake of medication.

Secondary Outcome Measures :

1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Up to Month 3 ]
   An adverse event (AE) is defined to be non-treatment-emergent if the onset date of the AE was clearly before the date of first HIV PEP administration, otherwise it is considered treatment-emergent.
2. Worst Sheehan Disability Scale (SDS) Score for the Safety Population [ Time Frame: Month 3 ]
   The Sheehan Disability Scale (SDS) assesses functional impairment in 3 inter-related domains: work/school, social and family life, using a rating scale for each item ranging from 0 (not at all) to 10 (extremely).
3. Percentage of Participants Who Developed Detectable HIV Antibodies [ Time Frame: At Month 3 ]
   Seroconversion rate of HIV antibodies while receiving HIV PEP evaluated as the percentage of participants who developed detectable HIV antibodies (defined as positive) and percentage of participants who had not developed detectable HIV antibodies (defined as negative). Per protocol (PP) population included all participants in mITT (defined as all participants who were assigned to receive randomized HIV PEP and were not discontinued due to confirmation of the negative HIV infection status of the index person) excluding participants with: No indication for HIV PEP; Initiation of PEP >72 hours after injury; Discontinuation of HIV PEP due to confirmation of HIV negative status of index person and if index person bears resistant virus against HIV PEP components prescribed; incorrect HIV PEP; no intake of medication.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Occupational injury and non-occupational exposure with documented human immunodeficiency virus (HIV) exposure, or potential for HIV exposure
• Indication for HIV postexposure prophylaxis (PEP), as determined by the treating physician and/or the investigator
• Women must be: postmenopausal (for at least 2 years), surgically sterile, using oral contraceptives
• Willing to continue HIV PEP for 28 days

Exclusion Criteria:

• Positive HIV rapid test
• History of liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastro intestinal, endocrine, neurologic, hematologic, rheumatologic, psychiatric, or metabolic disturbances
• Pregnant or breast-feeding
• Any condition that, in the opinion of the investigator, would compromise the well-being of the participant or the study or prevent the participant from meeting or performing study requirements

Contacts and Locations

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Locations

Germany
Berlin, Germany
Bonn, Germany
Dortmund, Germany
Dresden, Germany
Düsseldorf, Germany
Erlangen, Germany
Frankfurt, Germany
Freiburg, Germany
Hamburg, Germany
Köln, Germany
Magdeburg, Germany
Mainz, Germany
Mannheim, Germany
München, Germany
Regensburg, Germany
Stuttgart, Germany
Ulm, Germany

Sponsors and Collaborators

Janssen-Cilag G.m.b.H

Investigators

Study Director:	Janssen-Cilag G.m.b.H, Germany Clinical Trial	Janssen-Cilag G.m.b.H

More Information

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Responsible Party:	Janssen-Cilag G.m.b.H
ClinicalTrials.gov Identifier:	NCT01516970 History of Changes
Other Study ID Numbers:	CR018349; TMC114IFD3004 ( Other Identifier: Janssen-Cilag G.m.b.H, Germany ); 2011-001303-13 ( EudraCT Number )
First Posted:	January 25, 2012
Results First Posted:	October 11, 2016
Last Update Posted:	July 19, 2017
Last Verified:	June 2017

Studies a U.S. FDA-regulated Device Product:		No

Keywords provided by Janssen-Cilag G.m.b.H:

Human Immunodeficiency Virus (HIV) Post exposure prophylaxis; DRV/r; Occupational injury	Non-occupational exposure; Prezista; Darunavir/r

Additional relevant MeSH terms:

Immunologic Deficiency Syndromes; Acquired Immunodeficiency Syndrome; HIV Infections; Immune System Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Slow Virus Diseases; Ritonavir; Lopinavir; Darunavir; Zidovudine

Efavirenz; HIV Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors