Naïve HIV POC Monotherapy Trial

A Multicenter Phase 2a, Randomized, Double-blind, Placebo-controlled, Proof-of-concept Trial to Determine the Antiviral Activity, Pharmacokinetics, Tolerability and Safety of RDEA806 in HIV-1 Positive, Antiretroviral naïve Subjects

The primary objective of the trial is:

• to evaluate the change from baseline in plasma viral load with placebo and one of up to 4 dose regimens of RDEA806.

The secondary objectives are:

Efficacy

• to describe the nadir of the plasma viral load
• to describe the DAVG
• to assess the proportion of subjects who reached a drop in viral load of 0.5 log, 1 log, or reach an undetectable viral load
• to assess the plasma viral load decay rate
• to evaluate immunologic changes (as measured by CD4 and CD8 cells)
• to evaluate the genotypic and phenotypic pattern of the virus Pharmacokinetics
• to evaluate the pharmacokinetics and the pharmacokinetic/pharmacodynamic relationship of RDEA806 Safety
• to evaluate the safety and tolerability of bid and qd dosing of RDEA806 as monotherapy

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Placebo; Drug: RDEA806 400 mg; Drug: RDEA806 600 mg; Drug: RDEA806 800 mg; Drug: RDEA806 1000 mg

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Hamburg, Germany, 20099
• United Kingdom
  • London, United Kingdom, SW109NH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Documented chronic HIV-1 infection
• HIV-1 plasma viral load at screening visit above 5000 HIV-1 RNA copies/ml
• Male, aged above 18 years and less than 65 years of age
• Adequate method of birth control
• Subject has never received an antiretroviral agent (NRTI, NNRTI, PI, entry inhibitor or integrase inhibitor) for the treatment of HIV and agrees not to start antiretroviral therapy prior to enrollment or subject has only received a short course of treatment for less than 14 days and has been off treatment for at least 8 weeks
• Subject has no primary mutation in the reverse transcriptase (RT) gene associated with resistance to RT inhibitors and no major mutation in the protease gene associated with resistance to PIs determined by genotypic resistance testing at screening

Exclusion Criteria:

• History or suspicion of alcohol or drug abuse which in the Investigator's opinion may lead to non-compliance
• CD4 count < 350 cells/mm3
• Life expectancy of less than 6 months
• Receipt of an investigational drug within 30 days prior to the trial drug administration
• Receipt of any vaccine within 30 days of screening visit
• Acute HIV-1 infection (seroconversion illness)
• Acute hepatitis A or acute or chronic hepatitis B or C infection
• Currently active acquired immune deficiency syndrome (AIDS)-defining illness (Category C conditions according to the Centers for Disease Control [CDC] Classification System for HIV Infection 1993)
• No clinically relevant laboratory abnormalities Renal impairment: serum creatinine > 1.5 x ULN
• Febrile illness within 120 hours prior to dosing
• History of severe drug allergy or hypersensitivity
• Significant cardiac dysfunction

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RDEA806 400 mg; Placebo or RDEA806 400 mg twice daily (BID) for 7 days and a single morning dose on Day 8.	Drug: Placebo; Placebo; Drug: RDEA806 400 mg
Experimental: RDEA806 600 mg; Placebo or RDEA806 600 mg once daily (QD) for 7 days with an additional dose on the morning of Day 8.	Drug: Placebo; Placebo; Drug: RDEA806 600 mg
Experimental: RDEA806 800 mg; Placebo or RDEA806 800 mg QD using enteric coated tablets for 7 days with an additional morning dose on Day 8.	Drug: Placebo; Placebo; Drug: RDEA806 800 mg
Experimental: RDEA806 1000 mg; Placebo or RDEA806 1000 mg QD using enteric coated tablets for 7 days with an additional dose on the morning of Day 8.	Drug: Placebo; Placebo; Drug: RDEA806 1000 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in HIV plasma viral load	9 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety will be assessed as adverse and HIV related events, clinical laboratory test results(hematology, chemistry, urinalysis), vital signs, 12-lead electrocardiograms (ECGs), and physical examination	22 days
Pharmacokinetics and Resistance	22 days

Collaborators and Investigators

• Sponsor: Ardea Biosciences, Inc.
• Investigators: Study Director: Vijay Hingorani, MD, PhD, Ardea Biosciences

Publications and helpful links

General Publications

• Moyle G, Boffito M, Stoehr A, Rieger A, Shen Z, Manhard K, Sheedy B, Hingorani V, Raney A, Nguyen M, Nguyen T, Ong V, Yeh LT, Quart B. Phase 2a randomized controlled trial of short-term activity, safety, and pharmacokinetics of a novel nonnucleoside reverse transcriptase inhibitor, RDEA806, in HIV-1-positive, antiretroviral-naive subjects. Antimicrob Agents Chemother. 2010 Aug;54(8):3170-8. doi: 10.1128/AAC.00268-10. Epub 2010 May 24.

Study record dates

Study Major Dates

• Study Start: January 1, 2008
• Primary Completion (Actual): June 1, 2008
• Study Completion (Actual): August 1, 2008

Study Registration Dates

• First Submitted: February 6, 2008
• First Submitted That Met QC Criteria: February 15, 2008
• First Posted (Estimate): February 18, 2008

Study Record Updates

• Last Update Posted (Estimate): January 28, 2014
• Last Update Submitted That Met QC Criteria: December 20, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: HIV; treatment naïve
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: RDEA806-201