Safety and Benefit Study of Droxidopa to Treat Patients With Intradialytic Hypotension

NCT00657046 | Completed Phase 2 Results

• 1 other identifier: Droxidopa IDH201
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

In clinical trials in Japan, droxidopa has been shown to be effective in affecting blood pressure changes upon orthostatic challenge in patients with autonomic dysfunction, as well as reducing the severity and frequency of symptoms of orthostatic hypotension in these patients. The efficacy of droxidopa in ameliorating symptoms in patients undergoing dialysis has also been demonstrated in the literature and clinical trials conducted in Japan. The current study will investigate the clinical efficacy of two different doses of droxidopa in patients with intradialytic hypotension over a 4 week treatment period with a placebo control. The clinical efficacy will be evaluated by changes in hypotension- related symptoms, as well as changes in blood pressure prior to, during and following, HD sessions as compared to their pre-treatment baseline values.

Conditions

Intradialytic Hypotension

Outcome Measures

Primary Outcomes (1)

• Change in Average Mean Arterial Blood Pressure During Hemodialysis

  Change between average baseline (visits 2-7) mean arterial blood pressure during hemodialysis and average treatment (visits 14-19) mean arterial blood pressure during hemodialysis. The calculation of MAP was based on the systolic (SBP) and diastolic (DBP) blood pressure measurements taken during each valid HD session, using the traditional formula: MAP = (SBP+2\*DBP)/3 for each time-point. The mean of the intradialytic measurements was calculated for each valid HD session, and these daily mean values were averaged across the visits within each period.

  6 weeks

Secondary Outcomes (5)

• Change in Average Mean Nadir Systolic Blood Pressures During Hemodialysis;

  6 weeks

• Change in the Number of Hypotension-induced Interventions During Hemodialysis (HD) Sessions;

  6 weeks

• Change in the Hypotension-induced Symptom Severity Score

  6 weeks

• Daily Symptoms Associated With Hemodialysis

  6 weeks

• Change in the Multidimensional Fatigue Inventory (MFI-20)

  6 weeks

Other Outcomes (1)

• Change in Systolic Blood Pressure From Pre-dialysis to Post-dialysis

  6 weeks

Study Arms (3)

1

ACTIVE COMPARATOR

Droxidopa at 400 mg (2 capsules each containing 200 mg droxidopa plus one capsule with Placebo)

Drug: Droxidopa; Drug: Placebo

2

ACTIVE COMPARATOR

Droxidopa at 600 mg (3 capsules each containing 200 mg droxidopa)

Drug: Droxidopa

3

PLACEBO COMPARATOR

Placebo (3 capsules with mannitol substituted for droxidopa)

Drug: Placebo

Interventions

Droxidopa DRUG

Capsules containing 200 mg droxidopa

1; 2

Placebo DRUG

Capsules with mannitol substituted for droxidopa

1; 3

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female and aged 18 years or over;
• Clinical diagnosis of ESRD;
• Demonstrated requirement to undergo maintenance HD 3 times per week for sessions at least 3 hours in duration;
• Medical history consistent with IDH existing for at least 1 month;
• Observed symptomatic intradialytic hypotension in 3 of 6 HD sessions during screening, as defined by as a decrease in systolic blood pressure by ≥20 mm Hg or a decrease in MAP by 10 mm Hg associated with symptoms that include: abdominal discomfort; yawning; sighing; nausea; vomiting; muscle cramps; restlessness; dizziness or fainting; and anxiety (definition according to: National Kidney Foundation 2007) ;
• Provide written informed consent to participate in the study and understand that they may withdraw their consent at any time without prejudice to their future medical care.

You may not qualify if:

• Currently taking ephedrine or midodrine;
• Patients taking ephedrine or midodrine may enroll after a minimum 7 day washout period
• Taking anti-hypertensive medication on the day of dialysis;
• Currently taking selective norepinephrine re-uptake inhibitors;
• Current known or suspected drug or substance abuse;
• Women of childbearing potential who are not using a medically accepted contraception;
• Subject Restrictions:
• Reproductive potential: Female subjects should be either post-menopausal (amenorrhea for at least 12 consecutive months), surgically sterile, or women of child-bearing potential (WOCP) who are using or agree to use acceptable methods of contraception. Acceptable contraceptives include intrauterine devices (IUDs), hormonal contraceptives (oral, depot, patch or injectable) and double barrier methods such as condoms or diaphragms with spermicidal gel or foam.
• For WOCP a urine/serum beta HCG pregnancy test must be conducted at screening and study termination, and a urine/serum pregnancy test must be conducted at baseline; the results must be negative at screening and at baseline. WOCP must be advised to use acceptable contraceptives throughout the study period and for 30 days after the last dose of investigational product. If hormonal contraceptives are used they should be taken according to the package insert. WOCP who are not currently sexually active must agree to use acceptable contraception, as defined above, if they decide to become sexually active during the period of the study and for 30 days after the last dose of investigational product.
• Sexually active males whose partner is a WOCP must agree to use condoms for the duration of the study and for 30 days after the last dose;
• Women who are pregnant or breast feeding;
• Known or suspected hypersensitivity to the study medication or any of its ingredients;
• Have active atrial fibrillation (within the last 6 months) or, in the investigator's opinion, have any other significant cardiac arrhythmia;
• Any other significant systemic, hepatic or cardiac illness;
• Have a history of closed angle glaucoma;

Sponsors & Collaborators

• Chelsea Therapeutics: lead

Study Sites (1)

Rogue Valley Dialysis

Medford, Oregon, 97504, United States

Location

MeSH Terms

Interventions

Droxidopa

Intervention Hierarchy (Ancestors)

Norepinephrine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Chief Scientific Officer
• Organization: Chelsea Therapeutics Inc.

hewitt@chelsearx.com

704-973-4202

Study Officials

• Rekha Halligan, MD

  Bayview Nephrology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2008
• First Posted: April 14, 2008
• Study Start: December 1, 2007
• Primary Completion: January 1, 2009
• Study Completion: January 1, 2009
• Last Updated: June 27, 2014
• Results First Posted: June 27, 2014

Record last verified: 2014-05

Locations

US (1)