Phase I Trial to Determine the Safety and Pharmacokinetics of CRS3123.

NCT02106338 | Completed Phase 1

• 2 other identifiers: 10-0009HHSN272201500007I
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Clostridium Difficile Infection

Keywords

follow-up to 10-0008, Clostridium difficile, dose-escalating, CRS3123

Outcome Measures

Primary Outcomes (7)

• The sequential review of reported adverse events

  Up to Day 29

• The changes from baseline in key ECG findings

  Up to Day 29

• The changes from baseline in vital sign measurements

  Up to Day 29

• The changes from baseline in findings on physical examination.

  Up to Day 29

• The changes from baseline of hematology test

  Up to Day 29

• The changes from baseline of urinalysis test

  Up to Day 29

• The changes from baseline of clinical chemistry test

  Up to Day 29

Secondary Outcomes (6)

• Urine CRS3123 concentrations at multiple specified time points following dose administration.

  Day 2, 4, 6, 8, 10-12

• Fecal CRS3123 concentrations before oral administration of CRS3123

  Day -1

• Plasma CRS3123 concentrations at multiple specified time points following dose administration.

  Day 2, 4, 6, 8, 10-12

• Fecal CRS3123 concentrations at multiple specified time points following dose administration

  Day 2, 4, 6, 8, 10-12

• Urine CRS3123 concentrations before oral administration of CRS3123

  Day -1

Study Arms (3)

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

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

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

Other: Placebo; Drug: CRS3123

Interventions

Placebo OTHER

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

Cohort A; Cohort B; Cohort C

CRS3123 DRUG

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.

Cohort A; Cohort B; Cohort C

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Quintiles Phase I Services - Overland Park

Overland Park, Kansas, 66211-1553, United States

Location

Related Publications (1)

• 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.

  PMID: 31685472 DERIVED

MeSH Terms

Conditions

Clostridium Infections

Interventions

REP 3123

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 13, 2014
• First Posted: April 8, 2014
• Study Start: June 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: June 13, 2016

Record last verified: 2014-09

Locations

US (1)