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
Overview
- Phase
- Phase 1
- Intervention
- Subcutaneous RB006 0.5 mg/kg
- Conditions
- Healthy Volunteer
- Sponsor
- Regado Biosciences, Inc.
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- Primary Outcome of this study using SC RB006 with and without RB007 in healthy volunteers was safety as determined by Treatment Emergent Adverse Events
- Status
- Completed
- Last Updated
- 12 years ago
Overview
Brief Summary
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)
Investigators
Eligibility Criteria
Inclusion Criteria
- •An Institutional Review Board (IRB)-approved informed consent was signed and dated prior to any study-related activities.
- •Subject was between the ages of 18 and 45 years, inclusive.
- •Subject was a female with a negative urine or serum pregnancy test or postmenopausal for at least 1 year prior to randomization.
- •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.
- •Subject had normal (or abnormal and clinically insignificant) laboratory values at Screening.
- •Subject was medically normal with no significant abnormal findings at the Screening physical examination.
- •Subject had the ability to understand the requirements of the study and a willingness to comply with all study procedures.
- •Subject had not consumed and agreed to abstain from taking any dietary supplements or nonprescription drugs
- •Subject had not consumed and agreed to abstain from taking any prescription drugs
- •Subject had not consumed alcohol-containing beverages for 3 days prior to CRU admission
Exclusion Criteria
- •Evidence or history of clinically significant oncologic, pulmonary, hepatic, gastrointestinal (GI), cardiovascular, hematologic, metabolic, neurological, immunologic, nephrologic, endocrine, or psychiatric disease.
- •Any evidence or history of intracranial bleeding, aneurysm, or thrombotic or hemorrhagic stroke.
- •Any known individual or family history of a bleeding diathesis or coagulopathy.
- •Active or expected menstruation during the Treatment Phase (females only).
- •History of thrombocytopenia associated with abnormal bleeding or risk of a bleeding event, or screening or baseline platelet count \<100,000/mm
- •History of thrombocytosis associated with a thrombotic event or risk for a thrombotic event, or screening or baseline platelet count \>600,000/mm
- •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.
- •Urinary tract bleeding within 3 months of CRU admission, including microscopic hematuria on screening or baseline urinalysis.
- •Unusual or prolonged bleeding (e.g., gum bleeding, nosebleeds, easy bruising), as documented on the Self-Reported Bleeding Questionnaire, at Screening.
- •Severe trauma, fracture, major surgery, or biopsy of a parenchymal organ within 3 months of CRU admission.
Arms & Interventions
Cohort 1
Cohort 1: 6 subjects received Subcutaneous RB006 0.5 mg/kg and 2 subjects received SC placebo
Intervention: Subcutaneous RB006 0.5 mg/kg
Cohort 1
Cohort 1: 6 subjects received Subcutaneous RB006 0.5 mg/kg and 2 subjects received SC placebo
Intervention: Placebo
Cohort 1-A
Cohort 1-A: 4 subjects received open-label Subcutaneous RB006 0.5 mg/kg
Intervention: Subcutaneous RB006 0.5 mg/kg
Cohort 2
Cohort 2: 6 subjects received Subcutaneous RB006 1.0 mg/kg and 2 subjects received SC placebo
Intervention: Subcutaneous RB006 1.0 mg/kg
Cohort 2
Cohort 2: 6 subjects received Subcutaneous RB006 1.0 mg/kg and 2 subjects received SC placebo
Intervention: Placebo
Cohort 3
Cohort 3: 6 subjects received Subcutaneous RB006 3.0 mg/kg and 2 subjects received SC placebo
Intervention: Subcutaneous RB006 3.0 mg/kg
Cohort 3
Cohort 3: 6 subjects received Subcutaneous RB006 3.0 mg/kg and 2 subjects received SC placebo
Intervention: Placebo
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
Intervention: Subcutaneous RB006 2.0 mg
Outcomes
Primary Outcomes
Primary Outcome of this study using SC RB006 with and without RB007 in healthy volunteers was safety as determined by Treatment Emergent Adverse Events
Time Frame: 10 days
Secondary Outcomes
- Outcome of this study using SC RB006 with and without RB007 in healthy volunteers was safety as determined by Serious Adverse Events(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(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)(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)