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Safety, Tolerability and PK/PD of RB006 in a Healthy Volunteer SAD (SC101)

4 juin 2013 mis à jour par: Regado Biosciences, Inc.

A Phase 1 Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RB006 Administered Subcutaneously, With and Without IV RB007, in Healthy Young Volunteers

This was a Phase 1a, single-center, double-blind, randomized, placebo-controlled study of the safety, tolerability, PK, and PD of single ascending doses of RB006 administered as an SC injection, with and without IV RB007 (an active control agent for RB006), in healthy young volunteers. The study originally planned to enroll 4 cohorts of 8 subjects each (N=32); however, upon review cohort (Cohort 1-A) was necessary in order to fully define the PK profile of SC RB006. Therefore, 36 subjects were enrolled in this study.

Each cohort was balanced by sex with no more than 2/3 of one sex enrolled in any particular cohort (i.e., 5 of 8 subjects in each cohort). No subject participated in >1 dose group, and progression to the next higher dose only occurred if the prior dose level was well tolerated, as assessed by a Safety Review Committee (SRC)

Aperçu de l'étude

Type d'étude

Interventionnel

Inscription (Réel)

36

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
      • Austin, Texas, États-Unis, 78744
        • PPD Development, LP

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:

  1. An Institutional Review Board (IRB)-approved informed consent was signed and dated prior to any study-related activities.
  2. Subject was between the ages of 18 and 45 years, inclusive.
  3. Subject was a female with a negative urine or serum pregnancy test or postmenopausal for at least 1 year prior to randomization.
  4. Subject had a body mass index (BMI) between 18 kg/m2 and 32 kg/m2 (weight/[height]2) and was ≥50 kg and ≤120 kg total body weight.
  5. Subject had normal (or abnormal and clinically insignificant) laboratory values at Screening.
  6. Subject was medically normal with no significant abnormal findings at the Screening physical examination.
  7. Subject had the ability to understand the requirements of the study and a willingness to comply with all study procedures.
  8. Subject had not consumed and agreed to abstain from taking any dietary supplements or nonprescription drugs
  9. Subject had not consumed and agreed to abstain from taking any prescription drugs
  10. Subject had not consumed alcohol-containing beverages for 3 days prior to CRU admission
  11. Subject had not consumed grapefruit or grapefruit juice within the 14 days prior to CRU admission
  12. Subject had not used tobacco or nicotine-containing products within 6 months prior to CRU admission

Exclusion Criteria:

  1. Evidence or history of clinically significant oncologic, pulmonary, hepatic, gastrointestinal (GI), cardiovascular, hematologic, metabolic, neurological, immunologic, nephrologic, endocrine, or psychiatric disease.
  2. Any evidence or history of intracranial bleeding, aneurysm, or thrombotic or hemorrhagic stroke.
  3. Any known individual or family history of a bleeding diathesis or coagulopathy.
  4. Active or expected menstruation during the Treatment Phase (females only).
  5. History of thrombocytopenia associated with abnormal bleeding or risk of a bleeding event, or screening or baseline platelet count <100,000/mm3.
  6. History of thrombocytosis associated with a thrombotic event or risk for a thrombotic event, or screening or baseline platelet count >600,000/mm3.
  7. Endoscopically confirmed peptic ulcer disease within 3 years of CRU admission or GI bleeding within 3 months of CRU admission, including a positive stool for occult blood at Screening or Baseline.
  8. Urinary tract bleeding within 3 months of CRU admission, including microscopic hematuria on screening or baseline urinalysis.
  9. Unusual or prolonged bleeding (e.g., gum bleeding, nosebleeds, easy bruising), as documented on the Self-Reported Bleeding Questionnaire, at Screening.
  10. Severe trauma, fracture, major surgery, or biopsy of a parenchymal organ within 3 months of CRU admission.
  11. Severe persistent hypertension (systolic pressure >180 mmHg or diastolic pressure >110 mmHg).
  12. Baseline hemoglobin <12.0 g/dL for males or <11.0 g/dL for females; prothrombin time (PT) greater than the ULN; or aPTT greater than the ULN.
  13. Clinically significant liver dysfunction (e.g., as evidenced by elevated liver function tests).
  14. Clinically significant renal dysfunction (e.g., estimated glomerular filtration rate <60 mL/min or serum creatinine >1.5 mg/dL).
  15. History of illicit drug abuse in the past year or current evidence of such abuse in the opinion of the Investigator.
  16. Positive findings on urine drug screen.
  17. Positive findings for human immunodeficiency virus, hepatitis B, and/or hepatitis C at Screening.
  18. Pregnant or lactating.
  19. Acute illness within 1 week of CRU admission.
  20. A history of alcohol abuse in the past year relative to CRU admission.
  21. Donated plasma within 7 days of study drug administration.
  22. Donated 1 or more pints of blood (or equivalent blood loss) within 6 weeks prior to study drug administration.
  23. Use of an investigational drug within 30 days prior to CRU admission or prior REG1 Anticoagulation System exposure.

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

  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Quadruple

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Autre: Cohort 1
Cohort 1: 6 subjects received Subcutaneous RB006 0.5 mg/kg and 2 subjects received SC placebo
Placebo
Autres noms:
  • SC Placebo
Subcutaneous RB006 0.5 mg/kg
Autres noms:
  • SC RB006
Autre: Cohort 1-A
Cohort 1-A: 4 subjects received open-label Subcutaneous RB006 0.5 mg/kg
Subcutaneous RB006 0.5 mg/kg
Autres noms:
  • SC RB006
Autre: Cohort 2
Cohort 2: 6 subjects received Subcutaneous RB006 1.0 mg/kg and 2 subjects received SC placebo
Placebo
Autres noms:
  • SC Placebo
Subcutaneous RB006 1.0 mg/kg
Autres noms:
  • SC RB006
Autre: Cohort 3
Cohort 3: 6 subjects received Subcutaneous RB006 3.0 mg/kg and 2 subjects received SC placebo
Placebo
Autres noms:
  • SC Placebo
Subcutaneous RB006 3.0 mg/kg
Autres noms:
  • SC RB006
Autre: Cohort 4

8 subjects received subcutaneous RB006 2.0 mg/kg as well as the following:

  • 4 subjects received an IV bolus injection of 1 mg/kg RB007 at 72 hours post-RB006 administration
  • 4 subjects received an IV bolus injection of 1 mg/kg RB007 at 24, 72, and 120 hours post-RB006 administration
  • Arm 1: 4 subjects received an IV bolus injection of 1 mg/kg RB007 at 72 hours post-RB006 administration
  • Arm 2: 4 subjects received an IV bolus injection of 1 mg/kg RB007 at 24, 72, and 120 hours post-RB006 administration.
Autres noms:
  • SC RB006

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Délai
Primary Outcome of this study using SC RB006 with and without RB007 in healthy volunteers was safety as determined by Treatment Emergent Adverse Events
Délai: 10 days
10 days

Mesures de résultats secondaires

Mesure des résultats
Délai
Outcome of this study using SC RB006 with and without RB007 in healthy volunteers was safety as determined by Serious Adverse Events
Délai: 10 days
10 days
Outcome of this study using SC RB006 with and without RB007 in healthy volunteers was pharmacodynamics as determined by change from baseline in aPTT
Délai: Pre-dose, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216 (and if applicable, 264) hours post RB006 dose
Pre-dose, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 48, 60, 72, 84, 96, 120, 144, 168, 216 (and if applicable, 264) hours post RB006 dose
Outcome of this study using SC RB006 with and without RB007 in healthy volunteers was pharmacokinetics as determined by Maximum Observed Plasma Concentration (Cmax)
Délai: Pre-dose, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 48, 60, 72, 84, 96, 120, 144, 168, and 216 (and if applicable, 264) hours post-RB006 dose
Pre-dose, 1, 2, 3, 6, 9, 12, 15, 18, 24, 30, 36, 48, 60, 72, 84, 96, 120, 144, 168, and 216 (and if applicable, 264) hours post-RB006 dose

Collaborateurs et enquêteurs

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

Les enquêteurs

  • Chercheur principal: Matthew M Medlock, MD, PPD

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

1 août 2009

Achèvement primaire (Réel)

1 décembre 2009

Achèvement de l'étude (Réel)

1 décembre 2009

Dates d'inscription aux études

Première soumission

2 juin 2013

Première soumission répondant aux critères de contrôle qualité

4 juin 2013

Première publication (Estimation)

7 juin 2013

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Estimation)

7 juin 2013

Dernière mise à jour soumise répondant aux critères de contrôle qualité

4 juin 2013

Dernière vérification

1 juin 2013

Plus d'information

Termes liés à cette étude

Autres numéros d'identification d'étude

  • REG1-CLINSC101

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 .

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