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

21 septembre 2016 mis à jour par: N&N Pharmaceuticals Inc.

Phase I Trial to Assess the Safety and Pharmacokinetics of a Single Ascending Dose (SAD) of N-Methanocarbathymidine (N-MCT) in Normal Volunteers

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.

Aperçu de l'étude

Statut

Inconnue

Les conditions

Description détaillée

This is a Phase 1 trial evaluating the safety and pharmacokinetics of N-MCT administered orally as a single ascending dose. Healthy male and female (non-pregnant, non-lactating) subjects ages 18-45, will be consented and allowed to participate in the study if upon screening they meet the inclusion / exclusion criteria.

Subjects will be enrolled into one of four cohort groups sequentially. Each of the six subjects in each group will receive doses sequentially within 48 hours between each dose increase (ie, the second subject in a group will not receive a dose until 48 hours after the first subject received a dose).

Cohort 1 (6 subjects, male & female) will receive 200 mg, Cohort 2 (6 subjects, male & female) will receive 400 mg, Cohort 3 (8 subjects, males and females, 2 placebo, 6 treated) will receive 800 mg and Cohort 4 (8 subjects, males and females, 2 placebo, 6 treated) will receive 1200 mg of N-MCT.

Each cohort will be completed and the safety data evaluated prior to initiating the next cohort. All subjects will have plasma and urine samples evaluated for N-MCT.

The PI of the protocol and the IDMC will review safety data (AEs), safety labs, vital signs, and findings through Day 7 for Cohort 1 before enrolling subjects in Cohort 2. Cohort 2 data through Day 7 will be reviewed accordingly by the PI and IDMC before enrolling subjects in Cohort 3. Cohort 3 data through Day 7 will be reviewed by the PI and the IDMC before enrolling subjects in Cohort 4.

However, prior to dose escalation to a new cohort as described above, GHUCCTS IRB will review and approve, in expedited review, the IDMC report upon which the decision to escalate the dose to a new cohort is based.

Type d'étude

Interventionnel

Inscription (Anticipé)

28

Phase

  • La phase 1

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

    • District of Columbia
      • Washington, District of Columbia, États-Unis, 20007
        • Georgetown University Hospital

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 45 ans (Adulte)

Accepte les volontaires sains

Oui

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

Subjects must meet all Inclusion Criteria to be included in the study:

  1. Healthy men and women 18 to 45 years of age, inclusive
  2. Ability to understand the consent process and study procedures
  3. Informed consent obtained and signed
  4. Comprehension of the protocol, as determined by the clinic personnel using a series of questions after explaining the procedures.
  5. Subjects agree to be available for all study visits.
  6. General good health, no current medical illness or clinically significant abnormal physical examination findings as determined by study physician investigators
  7. Negative past or current history of herpes virus infections, or no current use of antiviral medications for the treatment of herpes virus infections
  8. 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.
  9. 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.
  10. Negative urine toxicology screen for nicotine (Cotinine) for screening and on the day of admission to the inpatient phase.
  11. Negative breath alcohol screen and agreement not to consume alcohol for the duration of the study.
  12. 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].
  13. Agreement by subjects with reproductive potential to use highly effective contraception as described in protocol Section 4.1.1.
  14. 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.

Exclusion Criteria:

  • Subjects meeting any of the Exclusion Criteria at Baseline will be excluded from study participation.

    1. Medical conditions that preclude participation in the study as determined by the study physician investigators.

      Note: Condition that may preclude participation includes:

      1.1. 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

      1.2. 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

    2. Clinically significant abnormal electrocardiogram (ECG) at screening in the judgment of the investigator.
    3. Screening laboratory values outside the acceptable low and upper limits unless deemed NCS by the principal investigator or sub-investigator.
    4. Positive serology results for Hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV) or human immunodeficiency virus (HIV) antibodies
    5. Febrile illness with temperature documented >38°C within 7 days of dosing
    6. Pregnancy or breastfeeding
    7. Known hypersensitivity or allergic reaction(s) to study drug components, including ingredients present in the formulation and/or to other nucleoside analogue antiviral drugs.
    8. Have consumed any prohibited products or undergone any prohibited procedure listed in Table 3 within the indicated time frame.
    9. 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.
    10. 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.
    11. Any specific condition that, in the judgment of the Investigator, precludes participation because it could affect subject safety.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Recherche sur les services de santé
  • Répartition: Non randomisé
  • Modèle interventionnel: Affectation à un seul groupe
  • Masquage: Aucun (étiquette ouverte)

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Cohort 1
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.
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.
Autres noms:
  • N-MCT
  • NN-001
Expérimental: Cohort 2
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.
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.
Autres noms:
  • N-MCT
  • NN-001
Expérimental: Cohort 3
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.
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.
Autres noms:
  • N-MCT
  • NN-001
Two patients in Cohort 3 & 4 will receive placebo capsules which is mannitol filled into size 0 capsules.
Autres noms:
  • Placebo
Expérimental: Cohort 4
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.
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.
Autres noms:
  • N-MCT
  • NN-001
Two patients in Cohort 3 & 4 will receive placebo capsules which is mannitol filled into size 0 capsules.
Autres noms:
  • Placebo

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
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
Délai: Day 1- Day 7
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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Plasma Concentrations of N-MCT Measured Before and at Multiple Time Points After Oral administration
Délai: 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

Plasma levels of N-MCT will be measured before and at multiple time points after the oral administration.

Plasma drug concentrations will be obtained at the following time points: 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.

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
Délai: 0 - 4, 4 - 8, 8 - 12, and 12 - 24 hours post dose
Urine concentrations of N-MCT will be measured before and at multiple time points after the oral administration. Pooled urine samples for the measurement of N-MCT concentration will be collected over the following intervals: 0 - 4, 4 - 8, 8 - 12, and 12 - 24 hours post dose.
0 - 4, 4 - 8, 8 - 12, and 12 - 24 hours post dose

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Les enquêteurs

  • Directeur d'études: Aquilur Rahman, PhD, N&N Pharmaceuticals Inc.

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 avril 2016

Achèvement primaire (Anticipé)

1 décembre 2016

Achèvement de l'étude (Anticipé)

1 décembre 2016

Dates d'inscription aux études

Première soumission

27 avril 2016

Première soumission répondant aux critères de contrôle qualité

17 mai 2016

Première publication (Estimation)

19 mai 2016

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

22 septembre 2016

Dernière mise à jour soumise répondant aux critères de contrôle qualité

21 septembre 2016

Dernière vérification

1 septembre 2016

Plus d'information

Termes liés à cette étude

Autres numéros d'identification d'étude

  • N-MCT 329-15

Plan pour les données individuelles des participants (IPD)

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INDÉCIS

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