Study in Healthy Volunteers to Investigate the Safety, Tolerability and Pharmacokinetics of VM-1500

Phase I, Drug-drug Interaction Study in Healthy Volunteers to Investigate the Safety, Tolerability and Pharmacokinetics of VM-1500 When Administered Orally, in Combination With Raltegravir or Darunavir

A randomized single dose, drug-drug interaction study in healthy volunteers for VM - 1500 given alone or in combination with Raltegravir or Darunavir in a 3 arm approach. The parallel design is used due to the long half life for VM-1500.

Study Overview

• Status: Completed
• Conditions: HIV-infection
• Intervention / Treatment: Drug: VM-1500; Drug: Raltegravir; Drug: Darunavir; Drug: Ritonavir

Detailed Description

This drug-drug interaction study will not be done as a cross-over study due to the extreme long half life of the drug. The 24 healthy subjects participating will be randomized to VM-1500 alone or VM-1500 in combination with Raltegravir or Darunavir in parallel arms.

For the cohort taking VM-1500 40 mg only just 4 subject will be enrolled as 6 subjects have been already on the same regimen in the trial before. Based on the parallel design it seems appropriate not to expose more healthy subjects than necessary. This means the available data of 6 subjects dosed with 40 mg VM-1500 alone will be matched.

Three groups of healthy subjects will be randomized to VM-1500 alone or VM-1500 in combination with Raltegravir or Darunavir (4:10:10). The healthy subjects will stay at the unit and receive 40 mg VM-1500 alone or VM1500 in combination with Raltegravir or Darunavir one time and PK blood samples at several time points will be collected. PK (trough level) blood samples will also be collected at visits on Days 2, 4,7, 14, 21, and on Day 36.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Thailand
  • Wanglang Road
    • Bangkok, Wanglang Road, Thailand, 10700
      • Faculty of Medicine, Siriraj Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Male subjects age between 18-45 years
2. Has been determined healthy by physical examination, assessment of drug abuse, medical history and vital signs
3. Has normal or acceptable results for the following screening tests: complete blood count (CBC), blood urea nitrogen (BUN), serum creatinine (Cr), fasting blood sugar (FBS), total bilirubin, aspartate aminotransferase (AST or SGOT), alanine aminotransferase (ALT or SGPT), alkaline phosphatase (ALP) and urinalysis.
4. Negative result for hepatitis A, hepatitis B, hepatitis C and HIV antibodies
5. Willing to participate and signed the informed consent form

Exclusion Criteria:

1. Hepatic or kidney disorders or any other disease or disorder which may in the opinion of the Investigator interfere with the results of the study or threaten the health of volunteers;
2. Drug intake (including herbal drugs) during the last month;
3. Active alcohol and/or drug abuse that, in the opinion of the site investigator, would interfere with adherence to study requirements;
4. Volunteers have taken any investigational drug at least 3 month prior to the start of the study;
5. Inability to understand the Protocol or follow its instructions.

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VM-1500 + Raltegravir; VM-1500 40 mg in combination with 400 mg Raltegravir	Drug: VM-1500; VM-1500 40 mg; Drug: Raltegravir; 400 mg Raltegravir
Experimental: VM-1500 +Darunavir; VM-1500 40 mg in combination with 600 mg Darunavir boosted with 100 mg Ritonavir	Drug: VM-1500; VM-1500 40 mg; Drug: Darunavir; Darunavir 600 mg; Drug: Ritonavir; Ritonavir 100 mg
Experimental: VM-1500; VM-1500 40 mg alone	Drug: VM-1500; VM-1500 40 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-related adverse events as assessed by Division of AIDS table for grading the severity of ADULT Adverse Events	Safety and tolerability of VM-1500 alone or in combination with raltegravir or darunavir in adult healthy subjects	36 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentrations of VM-1500 from Day 1 to Day 36	Plasma concentrations of VM-1500 given alone or in combination with raltegravir or darunavir	36 days
Plasma concentrations of VM1500A (active metabolite of VM1500) from Day 1 to Day 36	Plasma concentrations of VM-1500A alone or in combination with raltegravir or darunavir	36 days

Collaborators and Investigators

• Sponsor: Viriom
• Investigators: Principal Investigator: Somruedee Chatsiricharoenkul, MD, Acriles

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: June 18, 2015
• First Submitted That Met QC Criteria: June 30, 2015
• First Posted (Estimate): July 3, 2015

Study Record Updates

• Last Update Posted (Actual): October 4, 2018
• Last Update Submitted That Met QC Criteria: October 2, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• 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; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Raltegravir Potassium; Ritonavir; Darunavir
• Other Study ID Numbers: VM-1500-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No