Cette page a été traduite automatiquement et l'exactitude de la traduction n'est pas garantie. Veuillez vous référer au version anglaise pour un texte source.

A Safety and Tolerability Study of RJX Drug Product in Healthy Participants

14 avril 2020 mis à jour par: Reven Pharmaceuticals, Inc.

A Phase 1, Double-blind, Placebo-controlled, Randomized, Two-Part, Ascending Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Rejuveinix (RJX) in Healthy Participants

Designed as a single center, two-part, double-blind, placebo-controlled, randomized study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of RJX in healthy participants.

Aperçu de l'étude

Statut

Complété

Description détaillée

Part 1 is designed as a Single Ascending Dose (SAD) escalation study with 6 cohorts. Participants will undertake a screening visit between Day -21 and Day -1 to determine eligibility in the study. Those participants that meet the eligibility criteria will be admitted to the study site on the day prior to dosing (Day -1). Participants will receive a single dose of investigational product via IV infusion on Day 1. The first cohort will include the initial dosing of a sentinel group. The remaining participants in Cohort 1 will be dosed if, in the opinion of the investigator or delegate, there are no significant safety concerns identified in the sentinel participants within the first 24 hours after administration of the dose. Participants will be confined to the study site from Day -1 to Day 2 (24 hours post dose) and then required to return to the study site on Day 5 for a final follow up visit. Safety and PK assessments will be performed at selected time points throughout the study.

Part 2 is designed as a Multiple Ascending Dose (MAD) escalation study with 3 cohorts. The MAD arm of the study will commence in parallel with Cohort 6 of Part 1 following completion and review of safety and PK findings for Cohorts 1, 2, 3, 4, and 5 in Part 1. Participants will undertake a screening visit between Day -21 and Day -1 to determine eligibility in the study. Those participants that meet the eligibility criteria will be admitted to the study site on the day prior to dosing (Day -1). Participants will be randomly assigned to receive 1 of 3 proposed doses of investigational product via IV infusion every day for 7 days.Participants will be confined to the study site from Day -1 to Day 8 (24 hours post the final dose on Day 7) and then return to the study site on Day 12 for a final follow up visit. Safety and PK assessments will be performed at selected time points throughout the study.

Type d'étude

Interventionnel

Inscription (Réel)

76

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

    • Texas
      • San Antonio, Texas, États-Unis, 78209
        • ICON Early Phase Services

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 70 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

Inclusion Criteria:

  1. Healthy male and female participants aged 18 to 50 years inclusive (Cohort 1 to Cohort 5) or 51 to 70 years inclusive (Cohort 6 only),at the time of screening;
  2. Have a body mass index of 18 kg/m2 to 35 kg/m2, inclusive, at screening. In addition, weight cannot exceed 132 kg;
  3. Have negative screening assessment for viral hepatitis (hepatitis B or hepatitis C) and human immunodeficiency virus;
  4. Have negative routine urine drug screen and negative alcohol breath test at screening and Day -1;
  5. A female participant is eligible to participate if she is not pregnant,not breastfeeding, and at least 1 of the following conditions applies:

    1. Not of childbearing potential, defined as surgically sterile (documented hysterectomy, bilateral salpingectomy, tubal ligation or bilateral oophorectomy) or postmenopausal (no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient);
    2. Of childbearing potential and agrees to use 2 highly effective methods of contraception consistently during the treatment period and for at least 60 days after the last dose of investigational product;
  6. A male participant with a female partner of childbearing potential is eligible to participate if he agrees to use acceptable contraception during the treatment period and for at least 60 days after the last dose of investigational product and refrains from donating sperm during this period;
  7. Clinical laboratory test results within normal reference range for the population or investigator site, or any results that are judged to be not clinically significant by the investigator;
  8. Venous access sufficient to allow for blood sampling per the protocol;
  9. Reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures;
  10. Given written informed consent prior to any study procedures being performed

Exclusion Criteria:

  1. Have a history of clinically relevant cardiovascular disease, cancer, respiratory, hepatic, renal, gastrointestinal, endocrine (diabetes), hematological, or neurological disorders. Cohort 6 only - elderly participants with well controlled hypercholesterolemia on a stable dose of statin therapy or well controlled hypertension on a stable dose of antihypertensive medication(s), excluding diuretics, are allowed in Cohort 6 per the clinical judgment of the investigator.
  2. Have impaired renal function (defined as estimated glomerular filtration rate <90 cc/min/1.73m2 Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) creatinine equation at screening);
  3. Have a hsCRP above 1.25 × upper limit of normal;
  4. Have a clinically significant abnormality in the 12-lead electrocardiogram (ECG) or prolongation of corrected QT interval by Fredericia (QTcF) >440 ms in males and >450 ms in females;
  5. Have a supine systolic blood pressure (BP) greater than 140 mm Hg or a diastolic BP greater than 90 mm Hg. Up to 2 additional measurements may be undertaken after an appropriate resting interval at screening to confirm eligibility;
  6. Are currently enrolled in a clinical trial involving an investigational product, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study;
  7. Have received an investigational product within the last 3 months;
  8. Have suspected allergies to RJX, related compounds, or any components of the formulation, or history of significant atopy;
  9. Regularly use known drugs of abuse and/or show positive findings on drug screening or Day -1;
  10. Are women who are pregnant, intend to become pregnant, or are lactating;
  11. Participants will be excluded for using any of the following medication:

    • aspirin, multivitamins/vitamins or mineral preparations within 14 days prior to investigational product administration or 24 hours post the last infusion;
    • prescription, herbal or over the counter medications within 14 days of investigational product administration, with the exception of:

      • simple analgesics such as paracetamol, excluding aspirin
      • oral non-steroidal anti-inflammatory drugs
      • thyroid treatment, estrogen replacement therapy
      • hormonal contraception
      • Statins and anti-hypertensives are permitted for elderly participants in Cohort 6 (Part 1) - see inclusion criteria #1
  12. Have donated blood of more than 500 mL within 4 weeks prior to study enrollment;
  13. Have an average weekly alcohol intake that exceeds 21 units per week (males up to age 65) and 14 units per week (males over 65 and females) or are unwilling to stop alcohol consumption for 24 hours prior to study site admission (1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits). Participants must have a of negative alcohol breath test at Day -1 and no evidence of alcohol abuse in the previous 12 months, defined as > 21 weekly units for males up to age 65 and > 14 weekly units for males over 65 and females;
  14. Have smoked cigarettes in the last 90 days (including occasional smokers who have smoked more than 5 cigarettes per month within the last 90 days);
  15. In the opinion of the investigator or sponsor, are unsuitable for inclusion in the study;
  16. Are investigator site personnel directly affiliated with this study and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted;
  17. Are Reven employees or employees of third-party organizations involved with the study who require exclusion of their employees.

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: Science basique
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Double

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Expérimental: Part 1; Cohort 1; RJX or Placebo
Participants in Part 1; Cohort 1 will receive a single 0.024 mL/kg dose of RJX or matching placebo on Day 1.
RJX is an IV infusion formulation. The appropriate RJX dose is calculated based on mL/kg. The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained. Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline. To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
Expérimental: Part 1; Cohort 2; RJX or Placebo
Participants in Part 1; Cohort 2 will receive a single 0.076 mL/kg dose of RJX or matching placebo on Day 1.
RJX is an IV infusion formulation. The appropriate RJX dose is calculated based on mL/kg. The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained. Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline. To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
Expérimental: Part 1; Cohort 3; RJX or Placebo
Participants in Part 1; Cohort 3 will receive a single 0.240 mL/kg dose of RJX or matching placebo on Day 1.
RJX is an IV infusion formulation. The appropriate RJX dose is calculated based on mL/kg. The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained. Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline. To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
Expérimental: Part 1; Cohort 4; RJX or Placebo
Participants in Part 1; Cohort 4 will receive a single 0.5 mL/kg dose of RJX or matching placebo on Day 1.
RJX is an IV infusion formulation. The appropriate RJX dose is calculated based on mL/kg. The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained. Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline. To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
Expérimental: Part 1; Cohort 5; RJX or Placebo
Participants in Part 1; Cohort 5 will receive a single 0.759 mL/kg dose of RJX or matching placebo on Day 1.
RJX is an IV infusion formulation. The appropriate RJX dose is calculated based on mL/kg. The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained. Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline. To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
Expérimental: Part 1; Cohort 6; RJX or Placebo
Participants in Part 1; Cohort 6 will receive a single dose of RJX or matching placebo, to be determined following review of safety and PK data from Cohorts 1 to 5, on Day 1.
RJX is an IV infusion formulation. The appropriate RJX dose is calculated based on mL/kg. The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained. Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline. To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
Expérimental: Part 2; Cohort 1; RJX or Placebo

Participants in Part 2; Cohort 1 will receive a dose of RJX or matching placebo, determined based on the findings of Part 1, every day for 7 days.

The Part 2; Cohort 1 dose will be 1 log down from the maximum tolerated dose determined in Part 1 or at a dose determined to be safe and well tolerated in Part 1 with an acceptable PK profile.

RJX is an IV infusion formulation. The appropriate RJX dose is calculated based on mL/kg. The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained. Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline. To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
Expérimental: Part 2; Cohort 2; RJX or Placebo
Participants in Part 2; Cohort 2 will receive an escalated dose of RJX or matching placebo, determined based on the findings of Part 1, every day for 7 days.
RJX is an IV infusion formulation. The appropriate RJX dose is calculated based on mL/kg. The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained. Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline. To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
Expérimental: Part 2; Cohort 3; RJX or Placebo
Participants in Part 2; Cohort 3 will receive an escalated dose of RJX or matching placebo, determined based on the findings of Part 1, every day for 7 days.
RJX is an IV infusion formulation. The appropriate RJX dose is calculated based on mL/kg. The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained. Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline. To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Treatment-related Adverse Events (TEAE) Reporting of RJX
Délai: Up to Day 5 for Part 1 and Up to Day 12 for Part 2
Number of participants with indicated AEs receiving RJX as assessed by CTCAE v4 03
Up to Day 5 for Part 1 and Up to Day 12 for Part 2
Safety and Tolerability of RJX as Assessed by Electrocardiograms (ECGs).
Délai: Up to Day 2 for Part 1 and Up to Day 8 for Part 2
Number of participants with abnormal and clinically significant findings based on ECG.
Up to Day 2 for Part 1 and Up to Day 8 for Part 2
Safety and Tolerability of RJX as Assessed by Neurological Examinations.
Délai: Up to Day 5 for Part 1 and Up to Day 12 for Part 2
Number of participants with clinically significant values and actual changes from baseline of continuous neurological assessments.
Up to Day 5 for Part 1 and Up to Day 12 for Part 2

Collaborateurs et enquêteurs

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

Les enquêteurs

  • Chercheur principal: Dennis A Ruff, MD, ICON Early Phase Services

Publications et liens utiles

La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.

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 (Réel)

24 août 2018

Achèvement primaire (Réel)

15 janvier 2019

Achèvement de l'étude (Réel)

15 janvier 2019

Dates d'inscription aux études

Première soumission

29 août 2018

Première soumission répondant aux critères de contrôle qualité

18 septembre 2018

Première publication (Réel)

21 septembre 2018

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

27 avril 2020

Dernière mise à jour soumise répondant aux critères de contrôle qualité

14 avril 2020

Dernière vérification

1 avril 2020

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • RPI003

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

Essais cliniques sur Ischémie critique des membres

  • University Hospital of North Norway
    University of Tromso; Norwegian Muscle Disease Association (FFM); Norwegian... et autres collaborateurs
    Actif, ne recrute pas
    Dystrophies musculaires | Dystrophie musculaire des ceintures des membres | Dystrophie musculaire des ceintures des membres, type 2I | Limb Girdle Muscular Dystrophy R9 Liée à la FKRP
    Norvège

Essais cliniques sur RJX

3
S'abonner