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

Healthy Volunteer Clinical Trial

— SC101  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01872572
• Other study ID #: REG1-CLINSC101
• Status: Completed
• Phase: Phase 1
• First received: June 2, 2013
• Last updated: June 4, 2013
• Start date: August 2009
• Est. completion date: December 2009

Study information

• Verified date: June 2013
• Source: Regado Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Healthy Volunteer

Intervention

Drug:
• Subcutaneous RB006 0.5 mg/kg
Subcutaneous RB006 0.5 mg/kg
• Subcutaneous RB006 1.0 mg/kg
Subcutaneous RB006 1.0 mg/kg
• Subcutaneous RB006 3.0 mg/kg
Subcutaneous RB006 3.0 mg/kg
• Subcutaneous RB006 2.0 mg
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.
• Placebo
Placebo

Locations

Country	Name	City	State
United States	PPD Development, LP	Austin	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Regado Biosciences, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

Vavalle JP, Rusconi CP, Zelenkofske S, Wargin WA, Alexander JH, Becker RC. A phase 1 ascending dose study of a subcutaneously administered factor IXa inhibitor and its active control agent. J Thromb Haemost. 2012 Jul;10(7):1303-11. doi: 10.1111/j.1538-783 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Outcome of this study using SC RB006 with and without RB007 in healthy volunteers was safety as determined by Treatment Emergent Adverse Events		10 days	Yes
Secondary	Outcome of this study using SC RB006 with and without RB007 in healthy volunteers was safety as determined by Serious Adverse Events		10 days	Yes
Secondary	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	No
Secondary	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	No