Healthy Adult SubjectsPhase 1NCT01433835
Safety and Pharmacokinetics of Single Oral Doses of MBX-400 in Healthy Volunteers
A Phase 1 study testing MBX-400 in people with Healthy Adult Subjects, run by Microbiotix, Inc. at 1 site in United States.
Trial summary
The purpose of this study is to determine the safety and pharmacokinetics following a single oral dose of MBX-400. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Adult Subjects
- What is being tested?
- MBX-400
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2011to Sep 2012
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 32Show fewer
- 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
- Hemoglobin or hematocrit less than the lower limit of normal or greater than the upper limit of normal
- Alanine aminotransferase and aspartate aminotransferase greater than the upper limit of normal
- Prothrombin, partial thromboplastin time or international normalized ratio greater than 1.5 times the upper limit of normal
- Abnormal electrolyte values (i.e., sodium, potassium, carbon dioxide/bicarbonate, chloride and/or calcium outside of the reference range)
- Urinalysis showing presence of red blood cells, protein or microalbumin
- Cotinine level indicative of nicotine use
- Positive test for any drug of abuse on urine drug screen
- Positive serum pregnancy test if female
- Positive ethanol test
- Clinically significant vital signs
- Temperature above 100.0 °F
- Heart rate < 45 or > 100 beats per minute
- Respiratory rate < 12 or > 20 breaths per minute
- Systolic blood pressure < 100 or > 140 mm Hg OR diastolic blood pressure < 60 or > 90 mm Hg
- Known hypersensitivity to any ingredients in the MBX-400 capsules or Placebo capsules (e.g., MBX-400, microcrystalline cellulose, gelatin, titanium dioxide).
- Scheduled for surgical procedure during the study
- Investigator deems that subject has a condition that warrants exclusion from or is not suitable for the study
Trial locations and contacts
1 site in 1 country.
United States1 site
Frontage Clinical Research Center
Hackensack, New Jersey, 07601
About this study
The purpose of this study is to determine the safety and pharmacokinetics following a single oral dose of MBX-400.
Read the 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.
- Conditions
- Healthy Adult Subjects
- Being tested
- MBX-400, Placebo
- Keywords
- Cytomegalovirus, Antiviral, Safety, Healthy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MBX-400Drug
Also called ZSM-I-62, NSC D745998, Cyclopropavir (CPV), (Z)-9-{[2,2-bis-(hydroxymethyl)cyclopropylidene] methyl}guanine
Capsule(s) for oral administration as a single dose. Planned doses include: 35, 100, 350, 700, 1000 and 1350 mg.
PlaceboOther
Also called microcrystalline cellulose
Capsule(s) for oral administration as a single dose. Planned doses include: 35, 100, 350, 700, 1000 and 1350 mg.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Other: Placebo |
| MBX-400 | Experimental | Not described Receives: Drug: MBX-400 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety
Safety is evaluated by assessing the incidence and severity for 14 days following a single dose of MBX-400 including:
- Product-related serious and life-threatening adverse events
- Adverse events
- Laboratory data abnormalities and clinically significant changes
- Electrocardiogram abnormalities and clinically significant changes
- Physical exam abnormalities and clinically significant changes
- Vital signs abnormalities and clinically significant changes
Measured: 14 days
Area under the plasma concentration-time curve (AUC)
The following pharmacokinetic parameters will be evaluated:
- Maximum plasma concentration (Cmax)
- Time of maximum plasma concentration (Tmax)
- Area under the plasma concentration-time curve (AUC)
- Terminal plasma half-life (t1/2)
- Apparent plasma clearance (Cl/F)
- Apparent volume of distribution (Vd/F)
- Amount excreted in urine (Ae)
- Urinary clearance (Clu)
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2011 (estimated)
- Study startSep 2011
- Primary completionAug 2012
- Study completionSep 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Healthy Adult SubjectsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Microbiotix, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gregory J Tracey, MD, Principal investigator, Frontage Clinical Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01433835
- Sponsor's protocol ID
- 09-001
- Status last verified
- Aug 2013
- First submitted
- 11 Sep 2011
- Last updated
- 2 Aug 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 15561852Zhou 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.
PubMed 17454732Mhaske 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.
PubMed 19410465Li 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.
PubMed 20183619Gentry 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.
PubMed 20846508Chou 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.
PubMed 21041510James 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.
PubMed 21788463
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Pharmacokinetics of Single Oral Doses of MBX-400 in Healthy Volunteers
- ClinicalTrials.gov ID
- NCT01433835
- Acronym / sponsor ID
- 09-001
- Conditions
- Healthy Adult Subjects
- Keywords
- Cytomegalovirus, Antiviral, Safety, Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Microbiotix, Inc.Industry (pharma, biotech, devices)
- Study start
- Sep 2011
- Primary completion
- Aug 2012 (actual)
- Study completion
- Sep 2012 (actual)
- First posted
- 14 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Other: Placebo |
| MBX-400 | Experimental | Drug: MBX-400 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (32 listed)
- 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
- Clinically significant abnormal electrocardiogram (e.g., abnormal rhythm, abnormal intervals)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MBX-400Also: ZSM-I-62, NSC D745998, Cyclopropavir (CPV), (Z)-9-{[2,2-bis-(hydroxymethyl)cyclopropylidene] methyl}guanineCapsule(s) for oral administration as a single dose. Planned doses include: 35, 100, 350, 700, 1000 and 1350 mg. | Drug | MBX-400 |
| PlaceboAlso: microcrystalline celluloseCapsule(s) for oral administration as a single dose. Planned doses include: 35, 100, 350, 700, 1000 and 1350 mg. | Other | Placebo |
Primary outcome
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2013.
- Background: PubMed 15561852Kern 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.
- Background: PubMed 17454732Zhou 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.
- Background: PubMed 19410465Mhaske 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.
- Background: PubMed 20183619Li 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.
- Background: PubMed 20846508Gentry 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.
- Background: PubMed 21041510Chou 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.
- Background: PubMed 21788463James 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.
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Healthy Subjects
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gregory J Tracey, MD principal investigator
Frontage Clinical Research Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MBX-400 in people with Healthy Adult Subjects, run by Microbiotix, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety (time frame: 14 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01433835, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2013.