Evaluating the Safety and Plasma Levels of N-Methanocarbathymidine (N-MCT) in Normal Patients

NCT02778386 | Unknown Phase 1 DMC

• 1 other identifier: N-MCT 329-15
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase I evaluation of N-MCT in normal volunteers requires sequentially increased doses. At each dose level, the safety and pharmacokinetic will be measured. This Phase I trial will have the dose range of N-MCT from 200mg - 1200mg per patient.

Conditions

Toxicity

Outcome Measures

Primary Outcomes (1)

• The Safety and Tolerability of N-MCT Evaluated By The Sequential Review of Reported Adverse Events (AEs) and Changes from Baseline in Findings on Physical Examination, Vital Sign Measurements, and Safety Laboratory Tests

  The type, incidence, severity and relatedness to study drug of adverse events (AEs), and of abnormal findings on physical examination, vital sign measurements, and of safety laboratory tests (hematology, biochemistry, urinalysis) throughout the study period.

  Day 1- Day 7

Secondary Outcomes (2)

• Plasma Concentrations of N-MCT Measured Before and at Multiple Time Points After Oral administration

  Pre-Dose (0.000), 0.250, 0.500,0.750, 1.000, 1.500, 2.000, 2.500, 3.000, 4.000, 6.000, 8.000, 12.000, 24.000 and 48.000 hours

• Urine Concentrations of N-MCT Measured Before and at Multiple Time Points

  0 - 4, 4 - 8, 8 - 12, and 12 - 24 hours post dose

Study Arms (4)

Cohort 1

EXPERIMENTAL

6 subjects, male \& female will receive one dose each of 200 mg of N-Methanocarbathymidine orally in capsules. Each subject will be evaluated for any clinical signs of any toxicity.

Drug: N-Methanocarbathymidine

Cohort 2

EXPERIMENTAL

6 subjects, male \& female will receive one dose each of 400 mg of N-Methanocarbathymidine orally in capsules. Each subject will be evaluated for any clinical signs of any toxicity.

Drug: N-Methanocarbathymidine

Cohort 3

EXPERIMENTAL

8 subjects, males and females, 6 subjects will receive one dose each 800 mg of N-Methanocarbathymidine orally in capsules and 2 will receive a placebo capsule. Each subject will be evaluated for any clinical signs of any toxicity.

Drug: N-Methanocarbathymidine; Other: Placebo Capsule

Cohort 4

EXPERIMENTAL

8 subjects, males and females, 6 subjects will receive one dose each 1200 mg of N-Methanocarbathymidine orally in capsules and 2 will receive a placebo capsule. Each subject will be evaluated for any clinical signs of any toxicity.

Drug: N-Methanocarbathymidine; Other: Placebo Capsule

Interventions

N-Methanocarbathymidine DRUG

Patients will receive 200 mg, 400 mg, 800 mg or 1200 mg of N-Methanocarbathymidine administered orally on day 1 after subject's full screen for each cohort. Each dose will be completely evaluated for safety and pharmacokinetics. The doses of each cohort will be given after complete evaluation of the preceding cohort for any sign of toxicity. In the absence of no observed toxicity, the next cohort will be started in the normal subjects.

Also known as: N-MCT, NN-001

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Placebo Capsule OTHER

Two patients in Cohort 3 \& 4 will receive placebo capsules which is mannitol filled into size 0 capsules.

Also known as: Placebo

Cohort 3; Cohort 4

Eligibility Criteria

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

You may qualify if:

• Healthy men and women 18 to 45 years of age, inclusive
• Ability to understand the consent process and study procedures
• Informed consent obtained and signed
• Comprehension of the protocol, as determined by the clinic personnel using a series of questions after explaining the procedures.
• Subjects agree to be available for all study visits.
• General good health, no current medical illness or clinically significant abnormal physical examination findings as determined by study physician investigators
• Negative past or current history of herpes virus infections, or no current use of antiviral medications for the treatment of herpes virus infections
• Negative serum pregnancy test at screening and a negative serum pregnancy test on the day of admission to the inpatient phase for all female subjects of child bearing potential.
• Negative urine toxicology screen for marijuana, cocaine, opiates, amphetamines, phencyclidine, benzodiazepines, and barbiturates for screening and on the day of admission to the inpatient phase.
• Negative urine toxicology screen for nicotine (Cotinine) for screening and on the day of admission to the inpatient phase.
• Negative breath alcohol screen and agreement not to consume alcohol for the duration of the study.
• Body mass index (BMI) greater than or equal to 18.5 kg/m2 and less than or equal to 29.9 kg/m2 \[weight (kg)\]/ \[height (m)2\].
• Agreement by subjects with reproductive potential to use highly effective contraception as described in protocol Section 4.1.1.
• Willingness to avoid strenuous exercise for at least 72 hours prior to initial study drug administration and during the study to Day 7 visit.
• Note: Strenuous physical exercise includes long distance running \> 5 km/day, weight lifting, or any physical activity to which the subject is not accustomed.

You may not qualify if:

• Medical conditions that preclude participation in the study as determined by the study physician investigators.
• Note: Condition that may preclude participation includes:
• Vital signs that are outside the ranges in the table below, measured after at least 10 minutes rest:
• Blood Pressure (BP) 90-140/55-90 mmHg Pulse Rate (PR) 50 100 beats/min Tympanic Temperature (T) less than or equal to 37.6ºC Respiration Rate (RR) 12 to 20 breaths/minute
• Current diagnosis of pulmonary disease 1.3. Current diagnosis of asthma, which has required use of asthma medications within the past year 1.4. History of or current diagnosis of diabetes mellitus 1.5. Autoimmune disorder, such as systemic lupus erythematosus, Wegener's granulomatosis, rheumatoid arthritis 1.6. History of malignancy except low-grade skin cancer (i.e., basal cell carcinoma which has been surgically cured) 1.7. 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, cholecystectomy, irritable bowel syndrome, inflammatory bowel disease) 1.8. History of cardiac abnormalities including Wolff-Parkinson-White syndrome, dysrhythmias, or coronary artery disease 1.9. History of prolonged QT interval
• Clinically significant abnormal electrocardiogram (ECG) at screening in the judgment of the investigator.
• Screening laboratory values outside the acceptable low and upper limits unless deemed NCS by the principal investigator or sub-investigator.
• Positive serology results for Hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) or human immunodeficiency virus (HIV) antibodies
• Febrile illness with temperature documented \>38°C within 7 days of dosing
• Pregnancy or breastfeeding
• Known hypersensitivity or allergic reaction(s) to study drug components, including ingredients present in the formulation and/or to other nucleoside analogue antiviral drugs.
• Have consumed any prohibited products or undergone any prohibited procedure listed in Table 3 within the indicated time frame.
• 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.
• Use of any form of tobacco, including cigarette smoking, pipe smoking, oral tobacco, for 30 days before screening and for the duration of the study.
• Any specific condition that, in the judgment of the Investigator, precludes participation because it could affect subject safety.

Sponsors & Collaborators

• N&N Pharmaceuticals Inc.: lead

Study Sites (1)

Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

MeSH Terms

Interventions

(north)-methanocarbathymidine

Study Officials

• Aquilur Rahman, PhD

  N&N Pharmaceuticals Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 27, 2016
• First Posted: May 19, 2016
• Study Start: April 1, 2016
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: September 22, 2016

Record last verified: 2016-09

Locations

US (1)