Symptomatic Neurogenic Orthostatic Hypotension
Conditions
Keywords
Parkinson's Disease, Multiple System Atrophy, Pure Autonomic Failure, Primary Autonomic Failure, Dopamine Beta Hydroxylase Deficiency
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
Interventions
100, 200 or 300 mg
DRUGPlacebo capsules
Sponsors
H. Lundbeck A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time To Intervention | Randomization (Day 0) up to Week 12 | Kaplan-Meier estimates are presented for time to treatment intervention. The estimates represent the quartiles of the survival time, where 50% corresponds to the median time to need for treatment intervention. Need for intervention is defined as meeting ANY of the following criteria during the Double-Blind Treatment Period: * 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 * participant stops IMP or withdraws from study for patient-reported lack of efficacy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time To All-cause Discontinuation | Randomization (Day 0) up to Week 12 | Kaplan-Meier estimates are presented for time to all-cause discontinuation. The estimates represent the quartiles of the survival time, where 50% corresponds to the median time to discontinuation. Time to all-cause discontinuation was defined as the time from randomization to withdrawal or last contact date. |
| Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 Score | Randomization (Day 0); Weeks 2 to 12 | The OHSA scale was designed to rate symptoms occurring specifically as a result of low blood pressure (BP), on average, over the past week using an 11-point scale (0 to 10), with more severe symptoms scoring higher. A score of zero indicates that the symptom was not experienced, and 10 is the worst possible. The scale was used to assess six symptoms: 1) Dizziness, lightheadedness, feeling faint, or feeling like you might black out, 2) problems with vision, 3) weakness, 4) fatigue, 5) trouble concentrating, and 6) head/neck discomfort. Scores for each activity and a composite score for all six activities were tabulated. A mean negative change from baseline means that symptoms have improved. A mean positive change from baseline means that symptoms have gotten worse. |
| Number of Participants Who Needed Intervention During the 12-week Double-Blind Treatment Period | Randomization (Day 0) up to Week 12 | Need for intervention is defined as meeting ANY of the following criteria during the Double-Blind Treatment Period: * 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 * participant stops IMP or withdraws from study for patient-reported lack of efficacy. |
| Clinician-rated Clinical Global Impressions - Severity (CGI-S) | Weeks 2 to 12 | The CGI-S was developed to provide global measures of the severity of a participant's clinical condition during clinical studies. The CGI-S was utilized by both the clinician and the participant to provide an impression of the participant's current state of OH. The severity of the participant's current illness was rated by the clinician on a 7-point scale ranging from 1 (normal, no OH) to 7 (among those patients most extremely ill with OH). |
| Participant-rated CGI-S | Weeks 2 to 12 | The CGI-S was developed to provide global measures of the severity of a participant's clinical condition during clinical studies. The CGI-S was utilized by both the clinician and the participant to provide an impression of the participant's current state of OH. The severity of the participant's current illness was rated by the participant on a 7-point scale ranging from 1 (normal, no OH) to 7 (most extremely ill with OH). |
| Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Questionnaire (OHQ) Composite Score | Randomization (Day 0); Weeks 2 to 12 | The OHQ composite score was a mean of the OHSA composite and the Orthostatic Hypotension Daily Activity Scale (OHDAS) composite scores. The OHDAS was designed as a measure of quality of life. It uses an 11-point scale to assess whether orthostatic hypotension (OH) interfered with four types of activities: 1) standing for a short time, 2) standing for a long time, 3) walking for a short time, and 4) walking for a long time. A zero rating means that over the preceding week the activity was performed with no interference and a 10 rating means that orthostatic hypotension completely interfered with the activity. Scores for each activity and a composite score for all four activities were tabulated. A mean negative change from baseline means that symptoms have improved. A mean positive change from baseline means that symptoms have gotten worse. |
Countries
United States
Participant flow
Pre-assignment details
Participants were enrolled at 85 sites in the United States. 2 participants were enrolled but excluded from all analysis sets due to incorrect signing of the Informed Consent Form.
Participants by arm
| Arm | Count |
|---|---|
| Open-Label Droxidopa Active droxidopa 100, 200, 300, 400, 500, or 600 mg three times daily (TID) orally. During the Open-Label period, participants received 100 mg TID and their dose was raised (in 100 mg TID increments) at subsequent visits until optimal dose was determined. Participants then received active droxidopa 100, 200, 300, 400, 500, or 600 mg TID orally (equal to the participant's individual optimal dose). | 451 |
| Double-Blind Droxidopa Active droxidopa 100, 200, 300, 400, 500, or 600 mg TID orally (equal to participant's individual dose at the end of the Open-Label Period) | 126 |
| Double-Blind Placebo Matching placebo for droxidopa TID orally | 126 |
| Total | 703 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind (Up to 12 Weeks) | Adverse Event | 0 | 6 | 4 |
| Double-Blind (Up to 12 Weeks) | Did not meet randomization criteria | 0 | 1 | 0 |
| Double-Blind (Up to 12 Weeks) | Lost to Follow-up | 0 | 1 | 2 |
| Double-Blind (Up to 12 Weeks) | Met the need for intervention criteria | 0 | 31 | 27 |
| Double-Blind (Up to 12 Weeks) | Non-compliance | 0 | 1 | 1 |
| Double-Blind (Up to 12 Weeks) | Physician Decision | 0 | 0 | 1 |
| Double-Blind (Up to 12 Weeks) | Protocol Violation | 0 | 3 | 0 |
| Double-Blind (Up to 12 Weeks) | Withdrawal by Subject | 0 | 6 | 5 |
| Open-Label (Up to 16 Weeks) | Adverse Event | 53 | 0 | 0 |
| Open-Label (Up to 16 Weeks) | Did not meet Open-label entry criteria | 30 | 0 | 0 |
| Open-Label (Up to 16 Weeks) | Did not meet Randomization Criteria | 17 | 0 | 0 |
| Open-Label (Up to 16 Weeks) | Discontinued per medical monitor request | 2 | 0 | 0 |
| Open-Label (Up to 16 Weeks) | Incorrect signing of ICF | 2 | 0 | 0 |
| Open-Label (Up to 16 Weeks) | Lost to Follow-up | 4 | 0 | 0 |
| Open-Label (Up to 16 Weeks) | Met stopping criteria | 4 | 0 | 0 |
| Open-Label (Up to 16 Weeks) | Non-Compliance | 6 | 0 | 0 |
| Open-Label (Up to 16 Weeks) | Physician Decision | 11 | 0 | 0 |
| Open-Label (Up to 16 Weeks) | Protocol Violation | 9 | 0 | 0 |
| Open-Label (Up to 16 Weeks) | Site closing | 3 | 0 | 0 |
| Open-Label (Up to 16 Weeks) | Sponsor request to withdraw | 3 | 0 | 0 |
| Open-Label (Up to 16 Weeks) | Withdrawal by Subject | 56 | 0 | 0 |
Baseline characteristics
| Characteristic | Double-Blind Droxidopa | Double-Blind Placebo | Total | Open-Label Droxidopa |
|---|---|---|---|---|
| Age, Continuous Double-Blind Period | 64.8 years STANDARD_DEVIATION 16.1 | 64.6 years STANDARD_DEVIATION 15.76 | 64.7 years STANDARD_DEVIATION 15.9 | — |
| Age, Continuous Open-Label Period | — | — | 66.3 years STANDARD_DEVIATION 15.6 | 66.3 years STANDARD_DEVIATION 15.6 |
| Ethnicity (NIH/OMB) Double-Blind Period Hispanic or Latino | 32 Participants | 46 Participants | 78 Participants | — |
| Ethnicity (NIH/OMB) Double-Blind Period Not Hispanic or Latino | 94 Participants | 80 Participants | 174 Participants | — |
| Ethnicity (NIH/OMB) Double-Blind Period Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | — |
| Ethnicity (NIH/OMB) Open-Label Period Hispanic or Latino | — | — | 86 Participants | 86 Participants |
| Ethnicity (NIH/OMB) Open-Label Period Not Hispanic or Latino | — | — | 365 Participants | 365 Participants |
| Ethnicity (NIH/OMB) Open-Label Period Unknown or Not Reported | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Double-Blind Period American Indian or Alaska Native | 0 Participants | 1 Participants | 1 Participants | — |
| Race (NIH/OMB) Double-Blind Period Asian | 1 Participants | 3 Participants | 4 Participants | — |
| Race (NIH/OMB) Double-Blind Period Black or African American | 5 Participants | 4 Participants | 9 Participants | — |
| Race (NIH/OMB) Double-Blind Period More than one race | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Double-Blind Period Native Hawaiian or Other Pacific Islander | 2 Participants | 0 Participants | 2 Participants | — |
| Race (NIH/OMB) Double-Blind Period Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | — |
| Race (NIH/OMB) Double-Blind Period White | 118 Participants | 118 Participants | 236 Participants | — |
| Race (NIH/OMB) Open-Label Period American Indian or Alaska Native | — | — | 2 Participants | 2 Participants |
| Race (NIH/OMB) Open-Label Period Asian | — | — | 11 Participants | 11 Participants |
| Race (NIH/OMB) Open-Label Period Black or African American | — | — | 15 Participants | 15 Participants |
| Race (NIH/OMB) Open-Label Period More than one race | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Open-Label Period Native Hawaiian or Other Pacific Islander | — | — | 2 Participants | 2 Participants |
| Race (NIH/OMB) Open-Label Period Unknown or Not Reported | — | — | 0 Participants | 0 Participants |
| Race (NIH/OMB) Open-Label Period White | — | — | 421 Participants | 421 Participants |
| Sex: Female, Male Double-Blind Period Female | 56 Participants | 61 Participants | 117 Participants | — |
| Sex: Female, Male Double-Blind Period Male | 70 Participants | 65 Participants | 135 Participants | — |
| Sex: Female, Male Open-Label Period Female | — | — | 196 Participants | 196 Participants |
| Sex: Female, Male Open-Label Period Male | — | — | 255 Participants | 255 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 451 | 1 / 126 | 0 / 126 |
| other Total, other adverse events | 192 / 451 | 32 / 126 | 22 / 126 |
| serious Total, serious adverse events | 45 / 451 | 3 / 126 | 8 / 126 |
Outcome results
Primary
Time To Intervention
Kaplan-Meier estimates are presented for time to treatment intervention. The estimates represent the quartiles of the survival time, where 50% corresponds to the median time to need for treatment intervention. Need for intervention is defined as meeting ANY of the following criteria during the Double-Blind Treatment Period: * 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 * participant stops IMP or withdraws from study for patient-reported lack of efficacy.
Time frame: Randomization (Day 0) up to Week 12
Population: The Full-analysis Set (FAS) included all randomized participants who took at least one dose of IMP in the Double-Blind Treatment Period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Droxidopa | Time To Intervention | 25% | 52.00 Days |
| Double-Blind Droxidopa | Time To Intervention | 50% | NA Days |
| Double-Blind Droxidopa | Time To Intervention | 75% | NA Days |
| Double-Blind Placebo | Time To Intervention | 25% | 42.00 Days |
| Double-Blind Placebo | Time To Intervention | 50% | NA Days |
| Double-Blind Placebo | Time To Intervention | 75% | NA Days |
p-value: 0.80395% CI: [0.67, 1.62]Log Rank
Secondary
Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Questionnaire (OHQ) Composite Score
The OHQ composite score was a mean of the OHSA composite and the Orthostatic Hypotension Daily Activity Scale (OHDAS) composite scores. The OHDAS was designed as a measure of quality of life. It uses an 11-point scale to assess whether orthostatic hypotension (OH) interfered with four types of activities: 1) standing for a short time, 2) standing for a long time, 3) walking for a short time, and 4) walking for a long time. A zero rating means that over the preceding week the activity was performed with no interference and a 10 rating means that orthostatic hypotension completely interfered with the activity. Scores for each activity and a composite score for all four activities were tabulated. A mean negative change from baseline means that symptoms have improved. A mean positive change from baseline means that symptoms have gotten worse.
Time frame: Randomization (Day 0); Weeks 2 to 12
Population: The FAS included all randomized participants who took at least one dose of IMP in the Double-Blind Treatment Period. Here, 'Overall number of subjects analyzed' signifies participants evaluable for this outcome measure and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Droxidopa | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Questionnaire (OHQ) Composite Score | Week 12 | -0.08 Score on a scale | Standard Deviation 1.467 |
| Double-Blind Droxidopa | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Questionnaire (OHQ) Composite Score | Week 2 | 0.41 Score on a scale | Standard Deviation 1.673 |
| Double-Blind Droxidopa | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Questionnaire (OHQ) Composite Score | Week 4 | 0.21 Score on a scale | Standard Deviation 1.324 |
| Double-Blind Droxidopa | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Questionnaire (OHQ) Composite Score | Week 6 | 0.12 Score on a scale | Standard Deviation 1.257 |
| Double-Blind Droxidopa | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Questionnaire (OHQ) Composite Score | Week 8 | 0.10 Score on a scale | Standard Deviation 1.472 |
| Double-Blind Droxidopa | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Questionnaire (OHQ) Composite Score | Week 10 | -0.19 Score on a scale | Standard Deviation 1.174 |
| Double-Blind Placebo | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Questionnaire (OHQ) Composite Score | Week 8 | -0.25 Score on a scale | Standard Deviation 1.14 |
| Double-Blind Placebo | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Questionnaire (OHQ) Composite Score | Week 12 | -0.57 Score on a scale | Standard Deviation 1.163 |
| Double-Blind Placebo | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Questionnaire (OHQ) Composite Score | Week 6 | -0.05 Score on a scale | Standard Deviation 1.236 |
| Double-Blind Placebo | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Questionnaire (OHQ) Composite Score | Week 2 | 0.40 Score on a scale | Standard Deviation 1.509 |
| Double-Blind Placebo | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Questionnaire (OHQ) Composite Score | Week 10 | -0.56 Score on a scale | Standard Deviation 1.153 |
| Double-Blind Placebo | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Questionnaire (OHQ) Composite Score | Week 4 | 0.10 Score on a scale | Standard Deviation 1.281 |
Secondary
Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 Score
The OHSA scale was designed to rate symptoms occurring specifically as a result of low blood pressure (BP), on average, over the past week using an 11-point scale (0 to 10), with more severe symptoms scoring higher. A score of zero indicates that the symptom was not experienced, and 10 is the worst possible. The scale was used to assess six symptoms: 1) Dizziness, lightheadedness, feeling faint, or feeling like you might black out, 2) problems with vision, 3) weakness, 4) fatigue, 5) trouble concentrating, and 6) head/neck discomfort. Scores for each activity and a composite score for all six activities were tabulated. A mean negative change from baseline means that symptoms have improved. A mean positive change from baseline means that symptoms have gotten worse.
Time frame: Randomization (Day 0); Weeks 2 to 12
Population: The FAS included all randomized participants who took at least one dose of IMP in the Double-Blind Treatment Period. Here, 'Overall number of subjects analyzed' signifies participants evaluable for this outcome measure and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Droxidopa | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 Score | Week 10 | -0.3 Score on a scale | Standard Deviation 1.62 |
| Double-Blind Droxidopa | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 Score | Week 4 | 0.3 Score on a scale | Standard Deviation 1.83 |
| Double-Blind Droxidopa | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 Score | Week 12 | 0.1 Score on a scale | Standard Deviation 1.57 |
| Double-Blind Droxidopa | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 Score | Week 6 | 0.3 Score on a scale | Standard Deviation 1.77 |
| Double-Blind Droxidopa | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 Score | Week 2 | 0.5 Score on a scale | Standard Deviation 1.94 |
| Double-Blind Droxidopa | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 Score | Week 8 | 0.2 Score on a scale | Standard Deviation 1.93 |
| Double-Blind Placebo | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 Score | Week 2 | 0.5 Score on a scale | Standard Deviation 1.91 |
| Double-Blind Placebo | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 Score | Week 12 | -0.5 Score on a scale | Standard Deviation 1.52 |
| Double-Blind Placebo | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 Score | Week 10 | -0.5 Score on a scale | Standard Deviation 1.42 |
| Double-Blind Placebo | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 Score | Week 8 | 0.0 Score on a scale | Standard Deviation 1.5 |
| Double-Blind Placebo | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 Score | Week 4 | 0.3 Score on a scale | Standard Deviation 1.66 |
| Double-Blind Placebo | Change From Randomization To All Post-randomization Visits in Orthostatic Hypotension Symptom Assessment (OHSA) Item #1 Score | Week 6 | 0.1 Score on a scale | Standard Deviation 1.41 |
Secondary
Clinician-rated Clinical Global Impressions - Severity (CGI-S)
The CGI-S was developed to provide global measures of the severity of a participant's clinical condition during clinical studies. The CGI-S was utilized by both the clinician and the participant to provide an impression of the participant's current state of OH. The severity of the participant's current illness was rated by the clinician on a 7-point scale ranging from 1 (normal, no OH) to 7 (among those patients most extremely ill with OH).
Time frame: Weeks 2 to 12
Population: The FAS included all randomized participants who took at least one dose of IMP in the Double-Blind Treatment Period. Here, 'Overall number of subjects analyzed' signifies participants evaluable for this outcome measure and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Droxidopa | Clinician-rated Clinical Global Impressions - Severity (CGI-S) | Week 2 | 3.4 Score on a scale | Standard Deviation 1.24 |
| Double-Blind Droxidopa | Clinician-rated Clinical Global Impressions - Severity (CGI-S) | Week 4 | 3.1 Score on a scale | Standard Deviation 1.26 |
| Double-Blind Droxidopa | Clinician-rated Clinical Global Impressions - Severity (CGI-S) | Week 6 | 3.2 Score on a scale | Standard Deviation 1.07 |
| Double-Blind Droxidopa | Clinician-rated Clinical Global Impressions - Severity (CGI-S) | Week 8 | 3.2 Score on a scale | Standard Deviation 1.11 |
| Double-Blind Droxidopa | Clinician-rated Clinical Global Impressions - Severity (CGI-S) | Week 10 | 3.0 Score on a scale | Standard Deviation 1.15 |
| Double-Blind Droxidopa | Clinician-rated Clinical Global Impressions - Severity (CGI-S) | Week 12 | 3.0 Score on a scale | Standard Deviation 1.18 |
| Double-Blind Placebo | Clinician-rated Clinical Global Impressions - Severity (CGI-S) | Week 10 | 3.0 Score on a scale | Standard Deviation 1.19 |
| Double-Blind Placebo | Clinician-rated Clinical Global Impressions - Severity (CGI-S) | Week 2 | 3.3 Score on a scale | Standard Deviation 1.22 |
| Double-Blind Placebo | Clinician-rated Clinical Global Impressions - Severity (CGI-S) | Week 8 | 3.1 Score on a scale | Standard Deviation 1.24 |
| Double-Blind Placebo | Clinician-rated Clinical Global Impressions - Severity (CGI-S) | Week 4 | 3.3 Score on a scale | Standard Deviation 1.35 |
| Double-Blind Placebo | Clinician-rated Clinical Global Impressions - Severity (CGI-S) | Week 12 | 2.9 Score on a scale | Standard Deviation 1.09 |
| Double-Blind Placebo | Clinician-rated Clinical Global Impressions - Severity (CGI-S) | Week 6 | 3.2 Score on a scale | Standard Deviation 1.14 |
Secondary
Number of Participants Who Needed Intervention During the 12-week Double-Blind Treatment Period
Need for intervention is defined as meeting ANY of the following criteria during the Double-Blind Treatment Period: * 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 * participant stops IMP or withdraws from study for patient-reported lack of efficacy.
Time frame: Randomization (Day 0) up to Week 12
Population: The FAS included all randomized participants who took at least one dose of IMP in the Double-Blind Treatment Period.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind Droxidopa | Number of Participants Who Needed Intervention During the 12-week Double-Blind Treatment Period | 41 Participants |
| Double-Blind Placebo | Number of Participants Who Needed Intervention During the 12-week Double-Blind Treatment Period | 40 Participants |
Secondary
Participant-rated CGI-S
The CGI-S was developed to provide global measures of the severity of a participant's clinical condition during clinical studies. The CGI-S was utilized by both the clinician and the participant to provide an impression of the participant's current state of OH. The severity of the participant's current illness was rated by the participant on a 7-point scale ranging from 1 (normal, no OH) to 7 (most extremely ill with OH).
Time frame: Weeks 2 to 12
Population: The FAS included all randomized participants who took at least one dose of IMP in the Double-Blind Treatment Period. Here, 'Overall number of subjects analyzed' signifies participants evaluable for this outcome measure and Number analyzed is the number of participants evaluated at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Double-Blind Droxidopa | Participant-rated CGI-S | Week 8 | 3.2 Score on a scale | Standard Deviation 1.22 |
| Double-Blind Droxidopa | Participant-rated CGI-S | Week 6 | 3.2 Score on a scale | Standard Deviation 1.17 |
| Double-Blind Droxidopa | Participant-rated CGI-S | Week 10 | 3.1 Score on a scale | Standard Deviation 1.18 |
| Double-Blind Droxidopa | Participant-rated CGI-S | Week 2 | 3.4 Score on a scale | Standard Deviation 1.31 |
| Double-Blind Droxidopa | Participant-rated CGI-S | Week 4 | 3.2 Score on a scale | Standard Deviation 1.27 |
| Double-Blind Droxidopa | Participant-rated CGI-S | Week 12 | 3.1 Score on a scale | Standard Deviation 1.29 |
| Double-Blind Placebo | Participant-rated CGI-S | Week 4 | 3.3 Score on a scale | Standard Deviation 1.33 |
| Double-Blind Placebo | Participant-rated CGI-S | Week 8 | 3.1 Score on a scale | Standard Deviation 1.27 |
| Double-Blind Placebo | Participant-rated CGI-S | Week 2 | 3.2 Score on a scale | Standard Deviation 1.38 |
| Double-Blind Placebo | Participant-rated CGI-S | Week 6 | 3.1 Score on a scale | Standard Deviation 1.21 |
| Double-Blind Placebo | Participant-rated CGI-S | Week 12 | 2.8 Score on a scale | Standard Deviation 1.19 |
| Double-Blind Placebo | Participant-rated CGI-S | Week 10 | 3.0 Score on a scale | Standard Deviation 1.26 |
Secondary
Time To All-cause Discontinuation
Kaplan-Meier estimates are presented for time to all-cause discontinuation. The estimates represent the quartiles of the survival time, where 50% corresponds to the median time to discontinuation. Time to all-cause discontinuation was defined as the time from randomization to withdrawal or last contact date.
Time frame: Randomization (Day 0) up to Week 12
Population: The FAS included all randomized participants who took at least one dose of IMP in the Double-Blind Treatment Period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Double-Blind Droxidopa | Time To All-cause Discontinuation | 25% | 42.00 Days |
| Double-Blind Droxidopa | Time To All-cause Discontinuation | 50% | NA Days |
| Double-Blind Droxidopa | Time To All-cause Discontinuation | 75% | NA Days |
| Double-Blind Placebo | Time To All-cause Discontinuation | 25% | 51.00 Days |
| Double-Blind Placebo | Time To All-cause Discontinuation | 75% | NA Days |
| Double-Blind Placebo | Time To All-cause Discontinuation | 50% | NA Days |