NOX-100 for Preventing Hypotension During Hemodialysis

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Medinox, Inc.
Sponsor:
Collaborator:
Orient Europharma Co., Ltd.
Information provided by (Responsible Party):
Medinox, Inc.
ClinicalTrials.gov Identifier:
NCT01672008
First received: August 21, 2012
Last updated: March 27, 2014
Last verified: March 2014
  Purpose

This study is designed to evaluate the safety, tolerability and efficacy profile of NOX-100 to reduce intradialytic hypotension (IDH) in patients undergoing chronic hemodialysis (HD).


Condition Intervention Phase
Hypotension
Drug: NOX-100
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase IIa Study of Safety and Efficacy of NOX-100 for Preventing Hypotension in Patients During Hemodialysis Sessions

Resource links provided by NLM:


Further study details as provided by Medinox, Inc.:

Primary Outcome Measures:
  • Number of hypotension episode requiring intervention [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    Number reduction of symptomatic hypotension requiring intervention during HD with NOX-100 treatment.


Secondary Outcome Measures:
  • systolic blood pressure (SBP) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    Change in systolic blood pressure

  • Onset of symptoms of hypotension during HD [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    Time to onset of symptoms of hypotension during HD

  • The need for treatment intervention to raise BP. [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    Time to conduct a treatment intervention to raise BP


Estimated Enrollment: 70
Study Start Date: August 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NOX-100/Placebo

After enrollment, subjects will be randomly assigned to one of the following treatment sequences in a 1:1 ratio.

Sequence A: NOX-100 treatment phase followed by Placebo treatment phase Sequence B: Placebo treatment phase followed by NOX-100 treatment phase

Drug: NOX-100
Experimental: Placebo/NOX-100

After enrollment, subjects will be randomly assigned to one of the following treatment sequences in a 1:1 ratio.

Sequence A: NOX-100 treatment phase followed by Placebo treatment phase Sequence B: Placebo treatment phase followed by NOX-100 treatment phase

Drug: NOX-100

Detailed Description:

This is a 2-stage, prospective, randomized, double-blind, multi-dose, placebo-controlled, cross-over, phase IIa study to evaluate the safety, tolerability and efficacy profiles of NOX-100 to reduce the number of intradialytic hypotension episodes. At single-blind stage I, the eligible subject will receive a 1-week run-in period followed by a 1-week NOX-100 treatment in a dose of 0.4mg/kg/hr. To evaluate the clearance of NOX-100, plasma levels of NOX-100 at the end of the 1st dialysis and prior to the 2nd dialysis will be measured. An interim analysis will be undertaken after the completion of first stage. The following process should be conducted only if the plasma level of NOX-100 decreases by 90% or more in these patients and all safety data have been reviewed by the medical monitor.

At double blind stage II, patients will be randomized to one of the following treatment sequences in a 1:1 ratio.

  • Sequence A: NOX-100 treatment phase followed by Placebo treatment phase
  • Sequence B: Placebo treatment phase followed by NOX-100 treatment phase

After a 1-week placebo, the subjects will receive the two 4-week treatment (sequence A or sequence B)which are separated by 1-week wash-out. In the NOX-100 treatment phase, subjects will subsequently receive NOX-100 in doses of 1.2, 2.5, 5, and 10 mg/kg/hr at the first three dialysis sessions over each week. In the placebo treatment phase, subjects will receive comparative placebo for four weeks. For the first 20 subjects, the treatment dose could be escalated only after the individual safety data have been reviewed by an unblinded medical monitor.

To confirm if there is hepatic metabolism of NOX-100 between dialysis sessions, a pre-dialysis plasma level will be tested at the 2nd dialysis of Week 2, 5, 7 and 10 in the second stage.

In both stages, the blood pressure will be measured pre-HD, every 30 minutes during HD and post-HD for monitoring the hypotension episode. For safety assessment, all AE(s), SAE(s) and any signs/symptoms during HD will be recorded. The safety of study drug will be followed until 4 weeks after last treatment.

A Data and Safety Monitoring Board (DSMB) will be established prior to start of the trial and the DSMB meeting will be hold every 6~12 months during study period. Both medical monitor and DSMB will be responsible for safeguarding the interests of trial participants.

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males or non-pregnant, non-lactating females 20-80 years of age
  • Patients who are hemodialysis dependent with a history of end-stage renal disease (ESRD) for at least 3 months and need at least three HD sessions per week
  • History of intradialytic hypotension defined by at least 4 episodes with a fall in SBP of > 20 mmHg within 30 days prior to signing the ICF. At least two of the episodes must have caused symptoms requiring an intervention
  • No change in anti-hypertensive regimen for at least one month prior to enrollment/randomization
  • Be willing to sign the Informed Consent Form

Exclusion Criteria:

  • Subjects with adequate laboratory results at screening
  • Subjects with major psychiatric illness
  • Subjects with history of arrhythmia or severe congestive heart failure (New York Heart Association (NYHA) Class III and IV) within past 6 months, or those with hypoxic myocardium confirmed by EKG
  • Subjects with history of cirrhosis
  • Subjects with active infection disease defined as current treatment with anti-infection agent(s)
  • Subjects who need to receive nitrate and nitrite medication(s) (such as nitroglycerin, isosorbide mononitrate, and isosorbide dinitrate) for regular treatment
  • Subjects who need to receive unstable dose of midodrine, etilefrine or amezinium treatment within 7 days prior to receive the study treatment.
  • More than 14 drinks of alcohol per week
  • Use of any investigational drug or participation in any drug study within 30 days prior to enrollment/randomization
  • Any clinical condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk to participate in the study or confounds the ability to interpret data from the study as judged by the investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01672008

Contacts
Contact: Shirley Lin +886-2-2325-7621 ext 2922 Shirley.Lin@oppharma.com
Contact: Erwin Teng +886-2-2325-7621 ext 2921 erwin.teng@oppharma.com

Locations
Taiwan
China Medical University Hospital Recruiting
Taichung, Taiwan, 40447
Contact: Ya-Chun Hsiao    +886925-125-027    lovejojo0125@yahoo.com.tw   
Principal Investigator: Chiu-Ching Huang, MD         
Sponsors and Collaborators
Medinox, Inc.
Orient Europharma Co., Ltd.
Investigators
Study Chair: Monte Lai, Ph.D. Medinox, Inc.
  More Information

No publications provided

Responsible Party: Medinox, Inc.
ClinicalTrials.gov Identifier: NCT01672008     History of Changes
Other Study ID Numbers: NOX-100-ORIENT201
Study First Received: August 21, 2012
Last Updated: March 27, 2014
Health Authority: United States: Food and Drug Administration
Taiwan : Food and Drug Administration

Keywords provided by Medinox, Inc.:
NOX-100

Additional relevant MeSH terms:
Hypotension
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on September 16, 2014