Clostridium Difficile InfectionPhase 1NCT02106338
Phase I Trial to Determine the Safety and Pharmacokinetics of CRS3123.
A Phase 1 study testing CRS3123 in people with Clostridium Difficile Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
This is a Phase I, single center, randomized, placebo-controlled, double-blind, multiple ascending dose study to evaluate the safety and tolerability of CRS3123, a methionyl-tRNA synthetase inhibitor. 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 Infection
- 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
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2014to Dec 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 study procedures
- Informed consent obtained and signed
- 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 on the day of admittance to the inpatient phase I unit for all female subjects
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- Negative alcohol screen per phase I unit standard procedures (Breathalyzer) and urine toxicology screen for barbiturates, benzodiazepines, THC, cocaine, opiates, methamphetamines, TCA, methadone, MDMA (ecstasy), oxycodone, and amphetamines on screening and the day of admission to the inpatient phase.
- Agrees not to consume any alcohol 48 hours prior to admission or outpatient study visits.
- 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 the initiation of study drug administration. Female subjects must agree to the use of TWO reliable methods of contraception starting on screening day, while receiving study drug and for 4 weeks after the initiation of study drug administration, which can include: condoms, spermicidal gel, diaphragm, hormonal or non-hormonal intrauterine device, oral contraceptive pill, and depot progesterone injections. If a male subject is sexually active, the subject and his partner will each use at least one of the listed contraceptive methods. Women who have had a surgical sterilization procedure (tubal ligation, oophorectomy, or hysterectomy) are not required to use another birth control method
- Potential subjects must be willing to adhere to the following prohibitions and restrictions during the course of the study to be eligible for participation: - Strenuous exercise (e.g., long distance running > 5km/day, weight lifting, or any physical activity to which the subject is not accustomed) is to be avoided while confined to the Clinical Unit and for at least 72 hours prior to initial study drug administration and the scheduled follow-up visits Day 18 and 29.
Who cannot join
- Medical condition that precludes participation, including the following:
- Hypertension with confirmed systolic blood pressure >140 mmHg or confirmed diastolic blood pressure >90 mmHg, measured with vital signs after 10 - 15 minutes of rest. Abnormal measures may be repeated twice more (for a total of 3 times) at 5-10 minute intervals
- Current diagnosis of pulmonary disease
- Current diagnosis of asthma, which has required use of asthma medications within the past year
- History of or current diagnosis of diabetes mellitus
- Autoimmune disorder, such as lupus, Wegener's, rheumatoid arthritis
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- History of malignancy except low-grade skin cancer, (i.e., basal cell carcinoma, which has been surgically cured)
- Chronic renal, hepatic, or pulmonary disease or gastrointestinal tract 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)
- History of known Clostridium difficile infection
- History of cardiac rhythm abnormality including Wolff-Parkinson-White syndrome
- History of prolonged QT interval
- History of ovarian cysts
- Prolongation of QTcF interval (>450msec). Clinically significant abnormal electrocardiogram at screening in the judgment of the investigator, or based on the formal ECG reading by a Cardiologist; 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], with differential hemoglobin, platelets), Serum Chemistry (sodium, potassium, chloride, CO2, calcium, glucose, creatinine, BUN, CK, AST, ALT, AP, total bilirubin, protein, albumin, amylase, lipase), and Urinalysis (dipstick for glucose, protein and blood, and microscopic urinalysis if dipstick is abnormal and with provisons for re-testing in menstruating females in Section 7.16). If CK is above normal range at baseline, but not clinically significant, the subject can be included.
- Positive serology results for HIV, HBsAg, and 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 and documented, per Phase I Unit procedures, by the recruiter/interviewer assigned Phase 1 Unit personnel 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 before dosing. 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 based on reported medical history
- Any specific condition that, in the judgment of the Investigator, precludes participation because it could affect subject safety
- Subjects may not have donated blood in the 8 weeks prior to study entry and agree to not donate blood during and for 6 weeks following their active participation in the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
Quintiles Phase I Services - Overland Park
Overland Park, Kansas, 66211-1553
About this study
Official title: Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Phase I Trial to Determine the Safety and Pharmacokinetics of CRS3123 Administered Orally to Healthy Adults
This is a Phase I, single center, randomized, placebo-controlled, double-blind, multiple ascending dose study to evaluate the safety and tolerability of CRS3123, a methionyl-tRNA synthetase inhibitor. In this study, doses of 200, 400, and 600 mg, or 100mg are planned and will be given orally every 12 hours for 10 days. Up to 30 healthy male and female subjects 18 to 45 years, inclusive. The primary objective: of the study is to determine the safety and tolerability of escalating doses of CRS3123 following oral administration of multiple doses to healthy adults. The study duration is 46 weeks.
Read the detailed description
This is a Phase I, single center, randomized, placebo-controlled, double-blind, multiple ascending dose study to evaluate the safety and tolerability of CRS3123,a fully synthetic, oral, antimicrobial that targets methionyl-tRNA synthetase of gram-positive bacteria, including Clostridium difficile. This protocol will study oral doses of 200, 400, and 600 mg, or 100mg given orally every 12 hours for 10 days. Subjects will be divided into 3 cohorts, A, B, and C. Cohorts A and C will be given 200mg and 600mg of CRS3123 or placebo.The dose for cohort B and study progression and dose escalation to Cohorts B and C will require a full (planned) SMC review of all safety data obtained through Day 18. Should safety data review of the 200 mg dose result in an unfavorable safety profile, the study design allows for reduction in dose to 100 mg to be given in Cohort B. If this is the case, there will be no Cohort C. Up to 30 healthy male and female subjects 18 to 45 years, inclusive. The primary objective: of the study is to determine the safety and tolerability of escalating doses of CRS3123 following oral administration of multiple doses to healthy adults. The secondary objective will be to determine the plasma, urine and fecal concentrations and systemic exposure of CRS3123 after multiple oral doses.The study duration is 46 weeks.
- Conditions
- Clostridium Difficile Infection
- Being tested
- Placebo, CRS3123
- Keywords
- follow-up to 10-0008, Clostridium difficile, dose-escalating, CRS3123
- Medical subject headings
- Clostridium Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboOther
Placebo capsules have the same inert components as CRS3123; 2 subjects randomized in each cohorts recieve 200mg, 400mg; and 600mg, or 100mg are planned respectively given orally every 12 hours for 10 days
CRS3123Drug
CRS3123, a methionyl-tRNA synthetase inhibitor, formulated in 100 and 200 mg capsules; 8 subjects randomized in Cohorts A through C receive doses of 200 mg, 400 mg; and 600 mg or 100mg are planned respectively given orally every 12 hours for 10 days.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A | Experimental | 10 subjects (8 active, 2 placebo) receive a single oral dose of 200 mg CRS3123 or placebo every 12 hours for 10 days Receives: Other: Placebo; Drug: CRS3123 |
| Cohort B | Experimental | 10 subjects (8 active, 2 placebo) receive a single oral dose of 100 or 400 mg CRS3123 or placebo every 12 hours for 10 days Receives: Other: Placebo; Drug: CRS3123 |
| Cohort C | Experimental | 10 subjects (8 active, 2 placebo) receive a single oral dose of 600 mg CRS3123 or placebo every 12 hours for 10 days Receives: Other: Placebo; Drug: CRS3123 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The sequential review of reported adverse events
Measured: Up to Day 29
The changes from baseline in key ECG findings
Measured: Up to Day 29
The changes from baseline in vital sign measurements
Measured: Up to Day 29
The changes from baseline in findings on physical examination.
Measured: Up to Day 29
The changes from baseline of hematology test
Measured: Up to Day 29
The changes from baseline of urinalysis test
Measured: Up to Day 29
The changes from baseline of clinical chemistry test
Measured: Up to Day 29
Secondary outcomes (6)
Urine CRS3123 concentrations at multiple specified time points following dose administration.
Measured: Day 2, 4, 6, 8, 10-12
Fecal CRS3123 concentrations before oral administration of CRS3123
Measured: Day -1
Plasma CRS3123 concentrations at multiple specified time points following dose administration.
Measured: Day 2, 4, 6, 8, 10-12
Fecal CRS3123 concentrations at multiple specified time points following dose administration
Measured: Day 2, 4, 6, 8, 10-12
Urine CRS3123 concentrations before oral administration of CRS3123
Measured: Day -1
Plasma CRS3123 concentrations before oral administration of CRS3123
Measured: Day -1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2014 (estimated)
- Study startJun 2014
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Clostridium Difficile InfectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02106338
- Sponsor's protocol ID
- 10-0009
- Other IDs
- HHSN272201500007I
- Status last verified
- Sep 2014
- First submitted
- 13 Mar 2014
- Last updated
- 13 Jun 2016
- Results posted
- No
Publications
Lomeli BK, Galbraith H, Schettler J, Saviolakis GA, El-Amin W, Osborn B, Ravel J, Hazleton K, Lozupone CA, Evans RJ, Bell SJ, Ochsner UA, Jarvis TC, Baqar S, Janjic N. Multiple-Ascending-Dose Phase 1 Clinical Study of the Safety, Tolerability, and Pharmacokinetics of CRS3123, a Narrow-Spectrum Agent with Minimal Disruption of Normal Gut Microbiota. Antimicrob Agents Chemother. 2019 Dec 20;64(1):e01395-19. doi: 10.1128/AAC.01395-19. Print 2019 Dec 20.
PubMed 31685472
Study at a glance
From the registry record, last updated by the sponsor on 13 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Phase I Trial to Determine the Safety and Pharmacokinetics of CRS3123 Administered Orally to Healthy Adults
- ClinicalTrials.gov ID
- NCT02106338
- Acronym / sponsor ID
- 10-0009
- Conditions
- Clostridium Difficile Infection
- Keywords
- follow-up to 10-0008, Clostridium difficile, dose-escalating, CRS3123
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Jun 2014
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 8 Apr 2014 (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.
This is a Phase I, single center, randomized, placebo-controlled, double-blind, multiple ascending dose study to evaluate the safety and tolerability of CRS3123, a methionyl-tRNA synthetase inhibitor. In this study, doses of 200, 400, and 600 mg, or 100mg are planned and will be given orally every 12 hours for 10 days. Up to 30 healthy male and female subjects 18 to 45 years, inclusive. The primary objective: of the study is to determine the safety and tolerability of escalating doses of CRS3123 following oral administration of multiple doses to healthy adults. The study duration is 46 weeks.
Detailed description
This is a Phase I, single center, randomized, placebo-controlled, double-blind, multiple ascending dose study to evaluate the safety and tolerability of CRS3123,a fully synthetic, oral, antimicrobial that targets methionyl-tRNA synthetase of gram-positive bacteria, including Clostridium difficile. This protocol will study oral doses of 200, 400, and 600 mg, or 100mg given orally every 12 hours for 10 days. Subjects will be divided into 3 cohorts, A, B, and C. Cohorts A and C will be given 200mg and 600mg of CRS3123 or placebo.The dose for cohort B and study progression and dose escalation to Cohorts B and C will require a full (planned) SMC review of all safety data obtained through Day 18. Should safety data review of the 200 mg dose result in an unfavorable safety profile, the study design allows for reduction in dose to 100 mg to be given in Cohort B. If this is the case, there will be no Cohort C. Up to 30 healthy male and female subjects 18 to 45 years, inclusive. The primary objective: of the study is to determine the safety and tolerability of escalating doses of CRS3123 following oral administration of multiple doses to healthy adults. The secondary objective will be to determine the plasma, urine and fecal concentrations and systemic exposure of CRS3123 after multiple oral doses.The study duration is 46 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort A | Experimental | Other: Placebo, Drug: CRS312310 subjects (8 active, 2 placebo) receive a single oral dose of 200 mg CRS3123 or placebo every 12 hours for 10 days |
| Cohort B | Experimental | Other: Placebo, Drug: CRS312310 subjects (8 active, 2 placebo) receive a single oral dose of 100 or 400 mg CRS3123 or placebo every 12 hours for 10 days |
| Cohort C | Experimental | Other: Placebo, Drug: CRS312310 subjects (8 active, 2 placebo) receive a single oral dose of 600 mg CRS3123 or placebo every 12 hours for 10 days |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (11 listed)
- Men and women 18 to 45 years of age, inclusive
- Ability to understand the consent process and study procedures
- Informed consent obtained and signed
- 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
Key exclusion criteria (25 listed)
- Medical condition that precludes participation, including the following:
- Prolongation of QTcF interval (>450msec). Clinically significant abnormal electrocardiogram at screening in the judgment of the investigator, or based on the formal ECG reading by a Cardiologist; 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], with differential hemoglobin, platelets), Serum Chemistry (sodium, potassium, chloride, CO2, calcium, glucose, creatinine, BUN, CK, AST, ALT, AP, total bilirubin, protein, albumin, amylase, lipase), and Urinalysis (dipstick for glucose, protein and blood, and microscopic urinalysis if dipstick is abnormal and with provisons for re-testing in menstruating females in Section 7.16). If CK is above normal range at baseline, but not clinically significant, the subject can be included.
- Positive serology results for HIV, HBsAg, and HCV antibodies
- Febrile illness with temperature documented >38 degrees C within 7 days of dosing
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 |
|---|---|---|
| PlaceboPlacebo capsules have the same inert components as CRS3123; 2 subjects randomized in each cohorts recieve 200mg, 400mg; and 600mg, or 100mg are planned respectively given orally every 12 hours for 10 days | Other | Cohort A, Cohort B, Cohort C |
| CRS3123CRS3123, a methionyl-tRNA synthetase inhibitor, formulated in 100 and 200 mg capsules; 8 subjects randomized in Cohorts A through C receive doses of 200 mg, 400 mg; and 600 mg or 100mg are planned respectively given orally every 12 hours for 10 days. | Drug | Cohort A, Cohort B, Cohort C |
Primary outcome
The sequential review of reported adverse events
Time frame: Up to Day 29
The changes from baseline in key ECG findings
Time frame: Up to Day 29
The changes from baseline in vital sign measurements
Time frame: Up to Day 29
The changes from baseline in findings on physical examination.
Time frame: Up to Day 29
The changes from baseline of hematology test
Time frame: Up to Day 29
The changes from baseline of urinalysis test
Time frame: Up to Day 29
The changes from baseline of clinical chemistry test
Time frame: Up to Day 29
6 secondary outcomes
Urine CRS3123 concentrations at multiple specified time points following dose administration.
Time frame: Day 2, 4, 6, 8, 10-12
Fecal CRS3123 concentrations before oral administration of CRS3123
Time frame: Day -1
Plasma CRS3123 concentrations at multiple specified time points following dose administration.
Time frame: Day 2, 4, 6, 8, 10-12
Fecal CRS3123 concentrations at multiple specified time points following dose administration
Time frame: Day 2, 4, 6, 8, 10-12
Urine CRS3123 concentrations before oral administration of CRS3123
Time frame: Day -1
Plasma CRS3123 concentrations before oral administration of CRS3123
Time frame: Day -1
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 13 Jun 2016.
- Derived from this study: PubMed 31685472Lomeli BK, Galbraith H, Schettler J, Saviolakis GA, El-Amin W, Osborn B, Ravel J, Hazleton K, Lozupone CA, Evans RJ, Bell SJ, Ochsner UA, Jarvis TC, Baqar S, Janjic N. Multiple-Ascending-Dose Phase 1 Clinical Study of the Safety, Tolerability, and Pharmacokinetics of CRS3123, a Narrow-Spectrum Agent with Minimal Disruption of Normal Gut Microbiota. Antimicrob Agents Chemother. 2019 Dec 20;64(1):e01395-19. doi: 10.1128/AAC.01395-19. Print 2019 Dec 20.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 CRS3123 in people with Clostridium Difficile Infection, 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 11 inclusion and 25 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 13 Jun 2016. 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?
The sequential review of reported adverse events (time frame: Up to Day 29). The study lists 7 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 NCT02106338, 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 13 Jun 2016.