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Sustained Effect of Droxidopa in Symptomatic Neurogenic Orthostatic Hypotension (RESTORE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02586623
Recruitment Status : Recruiting
First Posted : October 26, 2015
Last Update Posted : May 5, 2020
Sponsor:
Information provided by (Responsible Party):
Lundbeck Northera Ltd.

Tracking Information
First Submitted Date  ICMJE October 23, 2015
First Posted Date  ICMJE October 26, 2015
Last Update Posted Date May 5, 2020
Actual Study Start Date  ICMJE February 2016
Estimated Primary Completion Date March 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 14, 2017)
Time-to-intervention [ Time Frame: Day 0 to Week 12 of double-blind period ]
Need for intervention is defined as meeting ANY of the following criteria during the Double-Blind Period:
  • Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 ≥2 unit worsening from Randomization (Visit 6) AND lack of efficacy as judged by the investigator; OR
  • OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) at 2 consecutive visits; OR
  • OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) at the visit before early discontinuation; OR
  • Patient stops IMP or withdraws from study for patient-reported lack of efficacy.
The timing of the need for intervention in the above criteria is defined as the first occurrence of a worsening of OHSA Item #1 by ≥ 2 units or when the patient stops taking IMP or withdraws due to a patient-reported lack of efficacy.
Original Primary Outcome Measures  ICMJE
 (submitted: October 23, 2015)
Time-to-intervention [ Time Frame: Randomization to week 12 ]
Need for intervention is defined as meeting ANY of the following criteria during the Double-Blind Period:
  • Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 ≥2 unit worsening from Randomization (Visit 6) AND lack of efficacy as judged by the investigator; OR
  • OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) at 2 consecutive visits; OR
  • OHSA Item #1 ≥2 unit worsening from Randomization (Visit 6) at the visit before early discontinuation; OR
  • Patient stops IMP or withdraws from study for patient-reported lack of efficacy.
The timing of the need for intervention in the above criteria is defined as the first occurrence of a worsening of OHSA Item #1 by ≥ 2 units or when the patient stops taking IMP or withdraws due to a patient-reported lack of efficacy.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2017)
  • Time to all cause discontinuation [ Time Frame: Day 0 to Week 12 of double-blind period ]
    Discontinuation for any reason
  • Mean change in OHSA item #1 score from Randomization (Visit 6) to all post-Randomization visits [ Time Frame: Day 0 to Week 12 of double-blind period ]
    Mean change in OHSA item #1 score from Randomization (Visit 6) to all post-Randomization visits
  • Mean change in Orthostatic Hypotension Questionnaire (OHQ) composite score from Randomization (Visit 6) to all post-Randomization visits [ Time Frame: Day 0 to Week 12 of double-blind period ]
    Mean change in Orthostatic Hypotension Questionnaire (OHQ) composite score from Randomization (Visit 6) to all post-Randomization visits
  • Clinician-rated Clinical Global Impressions - Severity (CGI-S) at all post-Randomization visits (Visits 7-12) [ Time Frame: Week 2 to Week 12 of double-blind period ]
    Clinician-rated Clinical Global Impressions - Severity (CGI-S) scores at all post-Randomization visits (Visits 7-12)
  • Patient-rated Clinical Global Impressions - Severity (CGI-S) at all post-Randomization visits (Visits 7-12) [ Time Frame: Week 2 to Week 12 of double-blind period ]
    Patient-rated Clinical Global Impressions - Severity (CGI-S) scores at all post-Randomization visits (Visits 7-12)
  • Proportion of patients who need intervention over the 12-week Double-Blind Treatment period [ Time Frame: Day 0 to Week 12 of double-blind period ]
    Proportion of patients who need intervention over the 12-week Double-Blind Treatment period
Original Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2015)
  • Time to all cause discontinuation [ Time Frame: Randomization to week 12 ]
  • Mean change in OHSA item #1 score from Randomization (Visit 6) to all post-Randomization visits [ Time Frame: Randomization to week 12 ]
  • Mean change in Orthostatic Hypotension Questionnaire (OHQ) composite score from Randomization (Visit 6) to all post-Randomization visits [ Time Frame: Randomization to week 12 ]
  • Clinician-rated Clinical Global Impressions - Severity (CGI-S) at all post-Randomization visits (Visits 7-12) [ Time Frame: Randomization to week 12 ]
  • Patient-rated CGI-S at all post-Randomization visits (Visits 7-12) [ Time Frame: Randomization to week 12 ]
  • Cumulative number of patients who need intervention over the 12-week Double-Blind Treatment period [ Time Frame: Randomization to week 12 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sustained Effect of Droxidopa in Symptomatic Neurogenic Orthostatic Hypotension
Official Title  ICMJE RESTORE: A Clinical Study of Patients With Symptomatic Neurogenic Orthostatic Hypotension to Assess Sustained Effects of Droxidopa Therapy
Brief Summary To evaluate the time to treatment intervention in patients with Parkinson's Disease (PD), Multiple System Atrophy (MSA), Pure Autonomic Failure (PAF), Non-Diabetic Autonomic Neuropathy (NDAN) or Dopamine Beta Hydroxylase (DBH) Deficiency who have been previously stabilized with droxidopa therapy for symptoms of neurogenic orthostatic hypotension (NOH) (dizziness, light-headedness, or feelings that they are about to black out)
Detailed Description

This is a multi-site, placebo-controlled, double-blind, randomized withdrawal, time to intervention study with a duration of up to 36 weeks, consisting of 5 periods:

Screening Period: up to 4 weeks duration; Open-Label Titration Period (Titration Period): up to 4 weeks duration; Open-Label Treatment Period (Open-Label Period): 12 weeks duration; Double-Blind Treatment Period (Double-Blind Period): 12 weeks duration; Safety Follow-Up Period: 4 weeks duration

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Symptomatic Neurogenic Orthostatic Hypotension
Intervention  ICMJE
  • Drug: Droxidopa capsules
    100, 200 or 300 mg
    Other Name: Northera
  • Drug: Placebo capsules
    Other Name: Placebo
Study Arms  ICMJE
  • Experimental: Open Label Period
    Active droxidopa 100, 200, 300, 400, 500, or 600 mg three times daily (TID) orally. During the Open Label Titration Period, patients will first receive 100 mg TID and their dose will be raised (in 100 mg increments) at subsequent visits until optimal dose is determined. During the Open Label Treatment Period, patients will receive active droxidopa100, 200, 300, 400, 500, or 600 mg three times daily (TID) orally (equal to the patient's individual dose at the end of the Open-Label Titration Period).
    Intervention: Drug: Droxidopa capsules
  • Placebo Comparator: Randomized Period
    Active droxidopa 100, 200, 300, 400, 500, or 600 mg three times daily (TID) orally (equal to patients individual dose at the end of the Open-Label Period) or matching placebo.
    Interventions:
    • Drug: Droxidopa capsules
    • Drug: Placebo capsules
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 23, 2015)
482
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 31, 2021
Estimated Primary Completion Date March 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 18 years or older and able to stand (with or without limited assistance)
  • Clinical diagnosis of symptomatic orthostatic hypotension associated with Primary Autonomic Failure (PD, MSA or PAF) or NDAN or DBH Deficiency
  • Score of at least 4 or greater on Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 (measured at Screening [Visit 1] and the first Titration Visit [Visit 2a] prior to dosing)
  • A documented drop of at least 20 millimeters of mercury (mmHg) in SBP, within 3 minutes of standing. This can either be documented in the patient history or assessed during Screening prior to the first Titration Visit (Visit 2a)
  • 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

Additional inclusion criteria for patients taking prescribed droxidopa prior to study entry:

Patients who are taking prescribed droxidopa therapy are eligible to participate in the study if they meet the other inclusion criteria and also have been on a stable dose of prescribed droxidopa for at least 2 weeks prior to the Screening Visit (Visit 1). In addition, they must meet either of the following at the Screening Visit (Visit 1):

  • The patient's Visit 1 OHSA Item #1 score is ≥ 7 AND the prescribed dose is ≤ 300 mg three times daily (TID); OR
  • The patient's Visit 1 OHSA Item #1 score is ≤6 AND worsens by ≥ 2 units when retested after washing out of droxidopa for at least 3 days

Exclusion Criteria:

  • In the investigator's opinion, the patient is not able to understand or cooperate with study procedures
  • Known or suspected alcohol or substance use disorder within the past 12 months (DSM-5 criteria)
  • Women who are pregnant or breastfeeding
  • Women of childbearing potential (WOCP) who are not using at least one method of contraception with their partner
  • Sustained supine hypertension greater than or equal to 180 mmHg systolic or 110 mmHg diastolic. Sustained is defined as the average of 3 observations each at least 10 minutes apart with the patient having been supine and at rest for at least 5 minutes prior to each measurement.
  • Untreated closed angle glaucoma
  • Diagnosis of hypertension that requires treatment with antihypertensive medications (short-acting antihypertensives to treat nocturnal supine hypertension are allowed in this study)
  • Any significant uncontrolled cardiac arrhythmia
  • History of myocardial infarction or stroke, within the past 2 years
  • Current unstable angina
  • Congestive heart failure (NYHA Class 3 or 4)
  • Diabetic autonomic neuropathy
  • History of cancer within the past 2 years other than a successfully treated, non-metastatic cutaneous squamous cell or basal cell carcinoma or cervical cancer in situ
  • Any major surgical procedure within the past 30 days
  • Currently receiving any investigational drug or have received an investigational drug within the past 28 days

Additional protocol defined exclusion criteria do apply

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Email contact via H. Lundbeck A/S LundbeckClinicalTrials@Lundbeck.com
Contact: Stephen W Gorny, MS 847-527-9583 STGO@Lundbeck.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02586623
Other Study ID Numbers  ICMJE 16306A
NOH402 ( Other Identifier: NOH402 )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Lundbeck Northera Ltd.
Study Sponsor  ICMJE Lundbeck Northera Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Email contact via H. Lundbeck A/S LundbeckClinicalTrials@Lundbeck.com
PRS Account Lundbeck Northera Ltd.
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP