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Clostridium Difficile ColitisPhase 1NCT01551004

Phase I Trial of a Single Dose of CRS3123

A Phase 1 study testing CRS3123 in people with Clostridium Difficile Colitis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Double-blind, randomized, placebo-controlled Phase I Trial to determine the safety and pharmokinetics of a single dose of CRS3123 in healthy adult volunteers. Forty healthy male and female subjects 18 to 45 years will be admitted in 5 dosing Cohorts, 8 subjects per Cohort. Read more about this study

Who is it for?
Ages 18 to 45 yearsHealthy volunteers can take part
Conditions the study is for
Clostridium Difficile Colitis
What is being tested?
CRS3123
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
40 participants
Where
1 siteUnited States
Study dates
22 May 2012to 21 Apr 2014
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 45 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • -Men and women 18 to 45 years of age, inclusive -Ability to understand the consent process and procedures -Informed consent obtained and signed -Comprehension of the protocol, which will be determined by the recruiter using a series of questions after explaining the procedures. Spanish speaking subjects will utilize a Spanish translation of the consent form with verbal discussion of the study's consent form and protocol by a JHU certified Spanish interpreter. -Subjects agree to be available for all study visits. Subjects will be asked if they have any travel plans, and whether staff could use alternate contact information that will be provided. -General good health, without current medical illness or clinically significant abnormal physical examination findings that classify the subject as other than healthy as determined by study investigators -Negative serum pregnancy test at screening and a negative urine pregnancy test on the day of admittance to the inpatient phase for all female subjects of child bearing potential -Negative urine toxicity screen for marijuana, cocaine metabolite, amphetamines, opiates, PCP, barbiturates, benzodiazepines -Negative breathalyzer -Body mass index (BMI) of < 35 [weight (kg)]/[height (m)^2] -Agreement by subjects with reproductive potential to use an adequate method of contraception during the study and for 4 weeks after study drug administration. Female subjects must agree to the use of TWO reliable methods of contraception while receiving study drug and for 4 weeks after study drug administration, which can include: condoms, spermicidal gel, diaphragm, hormonal or non-hormonal intrauterine device, surgical sterilization, oral contraceptive pill, depot progesterone injections, and sexual abstinence. If a male subject is sexually active, the subject and his partner mus agree to use at least one of the above listed contraceptive methods. -If the subject uses abstinence and becomes sexually active during the study, they must agree to use TWO if female and one if male, of the above listed contraceptive methods.

Who cannot join

  • -Medical condition that precludes participation, including the following: a. Hypertension with confirmed systolic blood pressure >140 mmHg or confirmed diastolic blood pressure >90 mmHg, measured after 10 - 15 minutes of rest b. Morbid obesity (BMI>35) c. Current diagnosis of pulmonary disease d. Current diagnosis of asthma, which has required use of asthma medications within the past year e. History of or current diagnosis of diabetes f. Autoimmune disorder, such as lupus, Wegener's, rheumatoid arthritis g. History of malignancy except low-grade skin cancer, (i.e., basal cell carcinoma has been surgically cured) h. Chronic renal, hepatic, or pulmonary disease condition that could interfere with the absorption of the study drug (e.g., surgical resection of significant proportions of the stomach or bowel, gastric bypass, gastric banding, irritable bowel syndrome, inflammatory bowel disease) i. History of known Clostridium difficile infection j. Blood donation within the previous 6 weeks k. History of cardiac rhythm abnormality including Wolff/Parkinson/White syndrome l. History of prolonged QT interval m. History of ovarian cysts -Prolongation of QTcB interval (i.e., confirmed QTcB interval >450 milliseconds) -Clinically significant abnormal electrocardiogram at screening in the judgment of the investigator, or based on the formal ECG reading; history of any cardiac abnormalities, including conduction abnormalities such as Wolff-Parkinson-White, dysrhythmias, or coronary artery disease -Laboratory values outside the expanded ranges in Appendix B for the following tests: blood cell counts (white blood cell counts [WBC], hemoglobin, platelets), serum chemistry (sodium, potassium, calcium, chloride, CO2, creatinine, glucose, BUN, AST, AP, ALT, total bilirubin, protein, albumin, amylase), urinalysis for glucose, protein and blood(with proviso for re-testing females in Section 6). If CK is above normal range at baseline, but not clinically significant, the subject can be included. -Positive serology results for HIV, HBsAg, or HCV antibodies -Febrile illness with temperature documented >38 degrees C within 7 days of dosing -Pregnancy or breastfeeding -Known allergic reactions to study drug components, including ingredients present in the formulation. -Treatment with another investigational drug within 30 days of dosing -Lack of ability to fully understand the informed consent. This will be determined by the recruiter/interviewer after explaining the consent and observing the subject reading the consent. -Ingestion of prescription medications, grapefruit juice, or St John's Wort starting 14 days or 5 half-lives before dosing, whichever is longer. Women may use oral contraceptives. -Ingestion of herbal supplements or over-the-counter medications starting 7 days before dosing -Use of any form of tobacco, including cigarette smoking, pipe smoking, or oral tobacco; if a former smoker or tobacco user, the subject must not have used tobacco for 30 days before screening -Any specific condition that, in the judgment of the Investigator, precludes participation because it could affect subject safety

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Johns Hopkins Bayview Medical Center - Infectious Diseases

    Baltimore, Maryland, 21224-2735

Other trials in United States

About this study

Official title: Randomized, Double-Blind, Placebo-Controlled, Single Ascending Dose Phase I Trial to Determine the Safety and Pharmacokinetics of CRS3123 Administered Orally to Healthy Adults

Double-blind, randomized, placebo-controlled Phase I Trial to determine the safety and pharmokinetics of a single dose of CRS3123 in healthy adult volunteers. Forty healthy male and female subjects 18 to 45 years will be admitted in 5 dosing Cohorts, 8 subjects per Cohort. Up to two alternates may be used per dosing Cohorts for study subjects that drop out. The primary objective of the study is to determine the safety and tolerability of escalating doses of CRS3123 following oral administration to healthy subjects.

Read the detailed description

This is a Phase I, multi-center, placebo-controlled, double-blind, dose-escalation study to evaluate the safety and tolerability of CRS3123, a methionyl-tRNA synthetase inhibitor. Since this is a FIH study of a new class of drugs, the maximum safe starting dose was estimated from the NOAEL from preclinical studies in accordance with FDA guidance documents (FDA Guidance for Industry, July 2005). A very low starting dose has been chosen. In the initial Cohorts, doses of 100, 200 and 400 will be given; all are below the estimated human starting dose. If any significant safety signals are encountered, the investigators will notify the SMC and call for a review. Dose escalation to Cohorts D and E will require a full SMC review of all safety data obtained through Day 7 for the preceding Cohorts. Forty healthy male and female subjects 18 to 45 years, inclusive, will be admitted for an inpatient study. Each subject will receive a single oral dose of CRS3123 or placebo. There will be 8 patients for each cohort (6 active, 2 placebo). The ascending doses are 100, 200, 400, 800 and 1200 mg respectively for cohorts A through E. The primary objective is the safety and tolerability of escalating doses of CRS3123 following oral administration to healthy subjects. The secondary objective is to assess whether there is measurable systemic exposure and if so, to determine the plasma pharmacokinetic characteristics of CRS3123 after a single oral dose.

Being tested
CRS3123, Placebo
Keywords
C. diff, C. difficile, Clostridium difficile, CRS3123
Medical subject headings
Enterocolitis, Pseudomembranous

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CRS3123Drug

    CRS3123, a methionyl-tRNA synthetase inhibitor, will be supplied in 100 and 200 milligram capsules. Subjects randomized to active drug in Cohorts A through E will receive 100 mg, 200 mg, 400 mg, 800 mg and 1200 mg respectively, as a single oral dose.

  • PlaceboOther

    Matching placebo capsules will be given to 2 subjects of each cohort.

Study groups in NCT01551004
Study groupRoleWhat they receive
Cohort AExperimental8 subjects (6 active, 2 placebo) receive a single oral dose of 100 mg CRS3123 or placebo
Receives: Drug: CRS3123; Other: Placebo
Cohort BExperimental8 subjects (6 active, 2 placebo) receive a single oral dose of 200 mg CRS3123 or placebo
Receives: Drug: CRS3123; Other: Placebo
Cohort CExperimental8 subjects (6 active, 2 placebo) receive a single oral dose of 400 mg CRS3123 or placebo
Receives: Drug: CRS3123; Other: Placebo
Cohort DExperimental8 subjects (6 active, 2 placebo) receive a single oral dose of 800 mg CRS3123 or placebo
Receives: Drug: CRS3123; Other: Placebo
Cohort EExperimental8 subjects (6 active, 2 placebo) receive a single oral dose of 1200 mg CRS3123 or placebo
Receives: Drug: CRS3123; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Changes from baseline in findings on physical examination.

    Measured: Day 0 to Day 28

  2. Changes from baseline in key ECG findings.

    Measured: Day 0 to Day 28

  3. Changes from baseline in safety laboratory tests (hematology, chemistry, urinalysis).

    Measured: Day 0 to Day 28

  4. Changes from baseline in vital sign measurements.

    Measured: Day 0 to Day 28

  5. Reported adverse events

    Measured: Day 0 to Day 28

Secondary outcomes (2)
  1. Pharmacokinetics of CRS3123 determined and compared by measuring plasma CRS3123 concentrations before oral administration of CRS3123 and at multiple specified time points following dose administration.

    Measured: Day 0 Pre-dose and at the following times after dosing: 15 and 30 minutes, and 1, 2, 3, 4, 6, 8, 10, 12, 24, 48, and 72 hrs.

  2. Pharmacokinetics of CRS3123 determined and compared by measuring urine CRS3123 concentrations before oral administration of CRS3123 and at multiple specified time points following dose administration.

    Measured: Day 0, 24 hour timed urine collection after dosing.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Mar 2012 (estimated)
  2. Study start22 May 2012
  3. Primary completion7 Apr 2014
  4. Study completion21 Apr 2014

Resources

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
Double blind
Who is masked
Participant, Investigator
Enrolment
40 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01551004
Sponsor's protocol ID
10-0008
Other IDs
HHSN272201500007I
Status last verified
26 Sep 2014
First submitted
8 Mar 2012
Last updated
25 Sep 2017
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Nayak SU, Griffiss JM, Blumer J, O'Riordan MA, Gray W, McKenzie R, Jurao RA, An AT, Le M, Bell SJ, Ochsner UA, Jarvis TC, Janjic N, Zenilman JM. Safety, Tolerability, Systemic Exposure, and Metabolism of CRS3123, a Methionyl-tRNA Synthetase Inhibitor Developed for Treatment of Clostridium difficile, in a Phase 1 Study. Antimicrob Agents Chemother. 2017 Jul 25;61(8):e02760-16. doi: 10.1128/AAC.02760-16. Print 2017 Aug.

    PubMed 28584140

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CRS3123 in people with Clostridium Difficile Colitis, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 1 inclusion and 1 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 25 Sep 2017. 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. 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?

Changes from baseline in findings on physical examination. (time frame: Day 0 to Day 28). The study lists 5 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 NCT01551004, which also lists 1 linked publication.

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 25 Sep 2017.

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