Safety and Pharmacokinetics of Single Oral Doses of MBX-400 in Healthy Volunteers

NCT01433835 | Completed Phase 1

• 1 other identifier: 09-001
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine the safety and pharmacokinetics following a single oral dose of MBX-400.

Conditions

Healthy Adult Subjects

Keywords

Cytomegalovirus; Antiviral; Safety; Healthy

Outcome Measures

Primary Outcomes (2)

• Safety

  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

  14 days

• Area under the plasma concentration-time curve (AUC)

  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)

  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

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Other: Placebo

MBX-400

EXPERIMENTAL

Drug: MBX-400

Interventions

MBX-400 DRUG

Capsule(s) for oral administration as a single dose. Planned doses include: 35, 100, 350, 700, 1000 and 1350 mg.

Also known as: ZSM-I-62, NSC D745998, Cyclopropavir (CPV), (Z)-9-{[2,2-bis-(hydroxymethyl)cyclopropylidene] methyl}guanine

MBX-400

Placebo OTHER

Capsule(s) for oral administration as a single dose. Planned doses include: 35, 100, 350, 700, 1000 and 1350 mg.

Also known as: microcrystalline cellulose

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.
• Recent illness requiring treatment within 1 month of screening
• History of renal failure or renal insufficiency
• Clinically significant abnormal electrocardiogram (e.g., abnormal rhythm, abnormal intervals)
• Clinically significant results of hematology, chemistry, coagulation studies or urinalysis, including, but not limited to the following:
• White blood cell count, red blood cell count or platelet count less than the lower limit of normal or greater than 1.5 times the upper limit of normal

Sponsors & Collaborators

• Microbiotix, Inc.: lead

Study Sites (1)

Frontage Clinical Research Center

Hackensack, New Jersey, 07601, United States

Location

Related Publications (7)

• Kern ER, Bidanset DJ, Hartline CB, Yan Z, Zemlicka J, Quenelle DC. Oral activity of a methylenecyclopropane analog, cyclopropavir, in animal models for cytomegalovirus infections. Antimicrob Agents Chemother. 2004 Dec;48(12):4745-53. doi: 10.1128/AAC.48.12.4745-4753.2004.

  PMID: 15561852 BACKGROUND

• Zhou S, Zemlicka J, Kern ER, Drach JC. Fluoroanalogues of anti-cytomegalovirus agent cyclopropavir: synthesis and antiviral activity of (E)- and (Z)-9-[2,2-bis(hydroxymethyl)-3-fluorocyclopropylidene]methyl-adenines and guanines. Nucleosides Nucleotides Nucleic Acids. 2007;26(3):231-43. doi: 10.1080/15257770701257210.

  PMID: 17454732 BACKGROUND

• Mhaske SB, Ksebati B, Prichard MN, Drach JC, Zemlicka J. Phosphonate analogues of cyclopropavir phosphates and their E-isomers. Synthesis and antiviral activity. Bioorg Med Chem. 2009 Jun 1;17(11):3892-9. doi: 10.1016/j.bmc.2009.04.020. Epub 2009 Apr 17.

  PMID: 19410465 BACKGROUND

• Li C, Gentry BG, Drach JC, Zemlicka J. Synthesis and enantioselectivity of cyclopropavir phosphates for cellular GMP kinase. Nucleosides Nucleotides Nucleic Acids. 2009 Sep;28(9):795-808. doi: 10.1080/15257770903172720.

  PMID: 20183619 BACKGROUND

• Gentry BG, Gentry SN, Jackson TL, Zemlicka J, Drach JC. Phosphorylation of antiviral and endogenous nucleotides to di- and triphosphates by guanosine monophosphate kinase. Biochem Pharmacol. 2011 Jan 1;81(1):43-9. doi: 10.1016/j.bcp.2010.09.005. Epub 2010 Sep 22.

  PMID: 20846508 BACKGROUND

• Chou S, Bowlin TL. Cytomegalovirus UL97 mutations affecting cyclopropavir and ganciclovir susceptibility. Antimicrob Agents Chemother. 2011 Jan;55(1):382-4. doi: 10.1128/AAC.01259-10. Epub 2010 Nov 1.

  PMID: 21041510 BACKGROUND

• James SH, Hartline CB, Harden EA, Driebe EM, Schupp JM, Engelthaler DM, Keim PS, Bowlin TL, Kern ER, Prichard MN. Cyclopropavir inhibits the normal function of the human cytomegalovirus UL97 kinase. Antimicrob Agents Chemother. 2011 Oct;55(10):4682-91. doi: 10.1128/AAC.00571-11. Epub 2011 Jul 25.

  PMID: 21788463 BACKGROUND

MeSH Terms

Interventions

cyclopropavir; microcrystalline cellulose

Study Officials

• Gregory J Tracey, MD

  Frontage Clinical Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2011
• First Posted: September 14, 2011
• Study Start: September 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: September 1, 2012
• Last Updated: August 2, 2013

Record last verified: 2013-08

Locations

US (1)