Safety and Pharmacokinetics of Single Oral Doses of MBX-400 in Healthy Volunteers
Overview
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Microbiotix, Inc.
- Enrollment
- 48
- Locations
- 1
- Primary Endpoint
- Safety
Overview
Brief Summary
The purpose of this study is to determine the safety and pharmacokinetics following a single oral dose of MBX-400.
Detailed Description
Cytomegalovirus (CMV; herpesvirus 5), a member of the betaherpesvirus subgroup, occurs as a benign infection in the majority of humans, with a 90% prevalence in the adult population1. However, CMV infection continues to be a major cause of morbidity and mortality in immunosuppressed patients, particularly recipients of solid organ or bone marrow transplants. CMV is also known for its association with severe blinding retinitis, pneumonia and gastrointestinal inflammation in AIDS patients. However, with the successful introduction of HAART (highly active anti-retroviral therapy), the problem of CMV infection in AIDS patients has decreased substantially. CMV remains the most important cause of congenital viral infection in the United States, and CMV infection of neonates is associated with deafness, mental retardation and mortality. In addition, CMV is a suspected pathogenic agent in cardiovascular disease and can persist in large-vessel endothelial cells and infect all cell types involved in cardiovascular lesions. CMV has been implicated in the restenosis of diseased coronary arteries following angioplasty and has been associated with myocarditis. In severely immunocompromised patients with CMV infection, prolonged antiviral therapy is often necessary, which increases the risk of resistant viruses. Currently available therapy has limitations that preclude their long-term use including toxicity, poor oral bioavailability and the development of drug-resistant strains. MBX-400 is a nucleoside analog that is structurally related to ganciclovir and acyclovir and is being developed for the possible use in the prevention and/or treatment of CMV. MBX-400, has been shown to be a potent inhibitor of viral DNA synthesis and therefore may be useful in treating and/or preventing CMV infection.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Male or female 18 to 65 years of age
- •Females must be surgically-sterilized or post-menopausal (defined as at least 1 year since last menses with follicle stimulating hormone (FSH) level indicating subject is post-menopausal)
- •Males must have undergone vasectomy
- •Able to understand study requirements, agrees to participate in the study and willing and able to provide informed consent (using an informed consent form in a language in which the subject is fluent)
- •Willing and able to stay in a clinical facility for up to 7 days
- •BMI of 18 to 32 kg/m2
- •Non-smoker or former smoker or user of nicotine-containing products (defined as someone who smoked or used nicotine-products one or more times a week for at least one month) who has not smoked for at least 3 months and has not used nicotine-containing products for at least 1 month and is willing to abstain from nicotine-containing products during the study
- •Has adequate venous access
- •Willing to abstain from alcohol and illicit drugs during the study
Exclusion Criteria
- •Participation in another clinical trial within 3 months of screening
- •Unwilling to comply with study procedures or cooperate with study personnel.
- •Donated blood or had significant blood loss (greater than 1 unit) within 3 months of screening
- •History of any of the following
- •Human immunodeficiency virus (HIV), cytomegalovirus (CMV), hepatitis B or hepatitis C infection
- •Alcohol or drug abuse
- •Anemia or bleeding disorders
- •Gastrointestinal disorders
- •Chronic illness
- •Regular medication use (prescription, over-the-counter or herbal; defined as more than once per week; except multivitamins) or use of medication (except multivitamins) within 1 week of screening.
Arms & Interventions
Placebo
Intervention: Placebo (Other)
MBX-400
Intervention: MBX-400 (Drug)
Outcomes
Primary Outcomes
Safety
Time Frame: 14 days
Safety is evaluated by assessing the incidence and severity for 14 days following a single dose of MBX-400 including: 1. Product-related serious and life-threatening adverse events 2. Adverse events 3. Laboratory data abnormalities and clinically significant changes 4. Electrocardiogram abnormalities and clinically significant changes 5. Physical exam abnormalities and clinically significant changes 6. Vital signs abnormalities and clinically significant changes
Area under the plasma concentration-time curve (AUC)
Time Frame: Predose and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 18, 24, 36, 48, 60, 72, 84 and 96 hours following dosing
The following pharmacokinetic parameters will be evaluated: 1. Maximum plasma concentration (Cmax) 2. Time of maximum plasma concentration (Tmax) 3. Area under the plasma concentration-time curve (AUC) 4. Terminal plasma half-life (t1/2) 5. Apparent plasma clearance (Cl/F) 6. Apparent volume of distribution (Vd/F) 7. Amount excreted in urine (Ae) 8. Urinary clearance (Clu)
Secondary Outcomes
No secondary outcomes reported