Trial Outcomes & Findings for Sustained Effect of Droxidopa in Symptomatic Neurogenic Orthostatic Hypotension (NCT NCT02586623)

Last Updated: 2023-08-23

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

453 participants

Primary outcome timeframe

Randomization (Day 0) up to Week 12

Results posted on

2023-08-23

Participant Flow

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.

Participant milestones

Participant milestones
Measure	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).	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)	Double-Blind Placebo Matching placebo for droxidopa TID orally
Open-Label (Up to 16 Weeks) STARTED	453	0	0
Open-Label (Up to 16 Weeks) Received at Least 1 Dose of Study Drug	451	0	0
Open-Label (Up to 16 Weeks) Safety Set	451	0	0
Open-Label (Up to 16 Weeks) COMPLETED	253	0	0
Open-Label (Up to 16 Weeks) NOT COMPLETED	200	0	0
Double-Blind (Up to 12 Weeks) STARTED	0	127	126
Double-Blind (Up to 12 Weeks) Received at Least 1 Dose of Study Drug	0	126	126
Double-Blind (Up to 12 Weeks) Full Analysis Set (FAS)	0	126	126
Double-Blind (Up to 12 Weeks) COMPLETED	0	78	86
Double-Blind (Up to 12 Weeks) NOT COMPLETED	0	49	40

Reasons for withdrawal

Reasons for withdrawal
Measure	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).	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)	Double-Blind Placebo Matching placebo for droxidopa TID orally
Open-Label (Up to 16 Weeks) Adverse Event	53	0	0
Open-Label (Up to 16 Weeks) Lost to Follow-up	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) Withdrawal by Subject	56	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) Incorrect signing of ICF	2	0	0
Open-Label (Up to 16 Weeks) Met stopping criteria	4	0	0
Open-Label (Up to 16 Weeks) Sponsor request to withdraw	3	0	0
Open-Label (Up to 16 Weeks) Discontinued per medical monitor request	2	0	0
Open-Label (Up to 16 Weeks) Site closing	3	0	0
Double-Blind (Up to 12 Weeks) Adverse Event	0	6	4
Double-Blind (Up to 12 Weeks) Lost to Follow-up	0	1	2
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
Double-Blind (Up to 12 Weeks) Met the need for intervention criteria	0	31	27
Double-Blind (Up to 12 Weeks) Did not meet randomization criteria	0	1	0

Baseline Characteristics

Data are being reported separately for the open-label and double-blind periods.

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Double-Blind Droxidopa n=126 Participants 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)	Double-Blind Placebo n=126 Participants Matching placebo for droxidopa TID orally
Time To Intervention 50%	NA Days Insufficient number of events occurred to calculate this value	NA Days Insufficient number of events occurred to calculate this value
Time To Intervention 25%	52.00 Days Interval 26.0 to 72.0	42.00 Days Interval 27.0 to 86.0
Time To Intervention 75%	NA Days Insufficient number of events occurred to calculate this value	NA Days Insufficient number of events occurred to calculate this value

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Double-Blind Droxidopa n=126 Participants 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)	Double-Blind Placebo n=126 Participants Matching placebo for droxidopa TID orally
Number of Participants Who Needed Intervention During the 12-week Double-Blind Treatment Period	41 Participants	40 Participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Double-Blind Droxidopa n=126 Participants 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)	Double-Blind Placebo n=126 Participants Matching placebo for droxidopa TID orally
Time To All-cause Discontinuation 25%	42.00 Days Interval 26.0 to 56.0	51.00 Days Interval 28.0 to Insufficient number of events occurred to calculate this value
Time To All-cause Discontinuation 50%	NA Days Insufficient number of events occurred to calculate this value	NA Days Insufficient number of events occurred to calculate this value
Time To All-cause Discontinuation 75%	NA Days Insufficient number of events occurred to calculate this value	NA Days Insufficient number of events occurred to calculate this value

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Double-Blind Droxidopa n=121 Participants 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)	Double-Blind Placebo n=124 Participants Matching placebo for droxidopa TID orally
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	0.5 Score on a scale Standard Deviation 1.91
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	0.3 Score on a scale Standard Deviation 1.66
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	0.1 Score on a scale Standard Deviation 1.41
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	0.0 Score on a scale Standard Deviation 1.50
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	-0.5 Score on a scale Standard Deviation 1.42
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	-0.5 Score on a scale Standard Deviation 1.52

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Double-Blind Droxidopa n=117 Participants 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)	Double-Blind Placebo n=122 Participants Matching placebo for droxidopa TID orally
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	0.40 Score on a scale Standard Deviation 1.509
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	-0.25 Score on a scale Standard Deviation 1.140
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	-0.56 Score on a scale Standard Deviation 1.153
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	-0.57 Score on a scale Standard Deviation 1.163
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	0.10 Score on a scale Standard Deviation 1.281
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	-0.05 Score on a scale Standard Deviation 1.236

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Double-Blind Droxidopa n=118 Participants 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)	Double-Blind Placebo n=120 Participants Matching placebo for droxidopa TID orally
Clinician-rated Clinical Global Impressions - Severity (CGI-S) Week 2	3.4 Score on a scale Standard Deviation 1.24	3.3 Score on a scale Standard Deviation 1.22
Clinician-rated Clinical Global Impressions - Severity (CGI-S) Week 4	3.1 Score on a scale Standard Deviation 1.26	3.3 Score on a scale Standard Deviation 1.35
Clinician-rated Clinical Global Impressions - Severity (CGI-S) Week 8	3.2 Score on a scale Standard Deviation 1.11	3.1 Score on a scale Standard Deviation 1.24
Clinician-rated Clinical Global Impressions - Severity (CGI-S) Week 10	3.0 Score on a scale Standard Deviation 1.15	3.0 Score on a scale Standard Deviation 1.19
Clinician-rated Clinical Global Impressions - Severity (CGI-S) Week 6	3.2 Score on a scale Standard Deviation 1.07	3.2 Score on a scale Standard Deviation 1.14
Clinician-rated Clinical Global Impressions - Severity (CGI-S) Week 12	3.0 Score on a scale Standard Deviation 1.18	2.9 Score on a scale Standard Deviation 1.09

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Double-Blind Droxidopa n=120 Participants 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)	Double-Blind Placebo n=123 Participants Matching placebo for droxidopa TID orally
Participant-rated CGI-S Week 4	3.2 Score on a scale Standard Deviation 1.27	3.3 Score on a scale Standard Deviation 1.33
Participant-rated CGI-S Week 6	3.2 Score on a scale Standard Deviation 1.17	3.1 Score on a scale Standard Deviation 1.21
Participant-rated CGI-S Week 10	3.1 Score on a scale Standard Deviation 1.18	3.0 Score on a scale Standard Deviation 1.26
Participant-rated CGI-S Week 12	3.1 Score on a scale Standard Deviation 1.29	2.8 Score on a scale Standard Deviation 1.19
Participant-rated CGI-S Week 2	3.4 Score on a scale Standard Deviation 1.31	3.2 Score on a scale Standard Deviation 1.38
Participant-rated CGI-S Week 8	3.2 Score on a scale Standard Deviation 1.22	3.1 Score on a scale Standard Deviation 1.27

Adverse Events

Open-Label Droxidopa

Serious events: 45 serious events

Other events: 192 other events

Deaths: 6 deaths

Double-Blind Droxidopa

Serious events: 3 serious events

Other events: 32 other events

Deaths: 1 deaths

Double-Blind Placebo

Serious events: 8 serious events

Other events: 22 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Open-Label Droxidopa n=451 participants at risk 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).	Double-Blind Droxidopa n=126 participants at risk 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)	Double-Blind Placebo n=126 participants at risk Matching placebo for droxidopa TID orally
Gastrointestinal disorders Nausea	9.5% 43/451 • Number of events 54 • From first dose to 30 days after last dose (Up to approximately 8 months)	0.79% 1/126 • Number of events 1 • From first dose to 30 days after last dose (Up to approximately 8 months)	0.79% 1/126 • Number of events 1 • From first dose to 30 days after last dose (Up to approximately 8 months)
General disorders Fatigue	5.3% 24/451 • Number of events 27 • From first dose to 30 days after last dose (Up to approximately 8 months)	2.4% 3/126 • Number of events 3 • From first dose to 30 days after last dose (Up to approximately 8 months)	0.79% 1/126 • Number of events 1 • From first dose to 30 days after last dose (Up to approximately 8 months)
Infections and infestations Urinary tract infection	5.8% 26/451 • Number of events 30 • From first dose to 30 days after last dose (Up to approximately 8 months)	7.9% 10/126 • Number of events 11 • From first dose to 30 days after last dose (Up to approximately 8 months)	4.0% 5/126 • Number of events 5 • From first dose to 30 days after last dose (Up to approximately 8 months)
Injury, poisoning and procedural complications Fall	10.9% 49/451 • Number of events 83 • From first dose to 30 days after last dose (Up to approximately 8 months)	6.3% 8/126 • Number of events 10 • From first dose to 30 days after last dose (Up to approximately 8 months)	4.0% 5/126 • Number of events 9 • From first dose to 30 days after last dose (Up to approximately 8 months)
Nervous system disorders Dizziness	8.6% 39/451 • Number of events 49 • From first dose to 30 days after last dose (Up to approximately 8 months)	5.6% 7/126 • Number of events 8 • From first dose to 30 days after last dose (Up to approximately 8 months)	4.0% 5/126 • Number of events 7 • From first dose to 30 days after last dose (Up to approximately 8 months)
Nervous system disorders Headache	15.3% 69/451 • Number of events 90 • From first dose to 30 days after last dose (Up to approximately 8 months)	3.2% 4/126 • Number of events 4 • From first dose to 30 days after last dose (Up to approximately 8 months)	5.6% 7/126 • Number of events 8 • From first dose to 30 days after last dose (Up to approximately 8 months)
Vascular disorders Hypertension	5.3% 24/451 • Number of events 27 • From first dose to 30 days after last dose (Up to approximately 8 months)	0.79% 1/126 • Number of events 1 • From first dose to 30 days after last dose (Up to approximately 8 months)	2.4% 3/126 • Number of events 4 • From first dose to 30 days after last dose (Up to approximately 8 months)

Additional Information

Email contact via

H. Lundbeck A/S

Phone: +45 36301311

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Open-Label Droxidopa n=451 Participants 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).	Double-Blind Droxidopa n=126 Participants 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)	Double-Blind Placebo n=126 Participants Matching placebo for droxidopa TID orally	Total n=703 Participants Total of all reporting groups
Age, Continuous Open-Label Period	66.3 years STANDARD_DEVIATION 15.60 • n=451 Participants • Data are being reported separately for the open-label and double-blind periods.	—	—	66.3 years STANDARD_DEVIATION 15.60 • n=451 Participants • Data are being reported separately for the open-label and double-blind periods.
Age, Continuous Double-Blind Period	—	64.8 years STANDARD_DEVIATION 16.10 • n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	64.6 years STANDARD_DEVIATION 15.76 • n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	64.7 years STANDARD_DEVIATION 15.90 • n=252 Participants • Data are being reported separately for the open-label and double-blind periods.
Sex: Female, Male Open-Label Period · Female	196 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.	—	—	196 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.
Sex: Female, Male Open-Label Period · Male	255 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.	—	—	255 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.
Sex: Female, Male Double-Blind Period · Female	—	56 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	61 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	117 Participants n=252 Participants • Data are being reported separately for the open-label and double-blind periods.
Sex: Female, Male Double-Blind Period · Male	—	70 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	65 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	135 Participants n=252 Participants • Data are being reported separately for the open-label and double-blind periods.
Ethnicity (NIH/OMB) Open-Label Period · Hispanic or Latino	86 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.	—	—	86 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.
Ethnicity (NIH/OMB) Open-Label Period · Not Hispanic or Latino	365 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.	—	—	365 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.
Ethnicity (NIH/OMB) Open-Label Period · Unknown or Not Reported	0 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.	—	—	0 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.
Ethnicity (NIH/OMB) Double-Blind Period · Hispanic or Latino	—	32 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	46 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	78 Participants n=252 Participants • Data are being reported separately for the open-label and double-blind periods.
Ethnicity (NIH/OMB) Double-Blind Period · Not Hispanic or Latino	—	94 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	80 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	174 Participants n=252 Participants • Data are being reported separately for the open-label and double-blind periods.
Ethnicity (NIH/OMB) Double-Blind Period · Unknown or Not Reported	—	0 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	0 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	0 Participants n=252 Participants • Data are being reported separately for the open-label and double-blind periods.
Race (NIH/OMB) Open-Label Period · American Indian or Alaska Native	2 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.	—	—	2 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.
Race (NIH/OMB) Open-Label Period · Asian	11 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.	—	—	11 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.
Race (NIH/OMB) Open-Label Period · Native Hawaiian or Other Pacific Islander	2 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.	—	—	2 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.
Race (NIH/OMB) Open-Label Period · Black or African American	15 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.	—	—	15 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.
Race (NIH/OMB) Open-Label Period · White	421 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.	—	—	421 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.
Race (NIH/OMB) Open-Label Period · More than one race	0 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.	—	—	0 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.
Race (NIH/OMB) Open-Label Period · Unknown or Not Reported	0 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.	—	—	0 Participants n=451 Participants • Data are being reported separately for the open-label and double-blind periods.
Race (NIH/OMB) Double-Blind Period · American Indian or Alaska Native	—	0 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	1 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	1 Participants n=252 Participants • Data are being reported separately for the open-label and double-blind periods.
Race (NIH/OMB) Double-Blind Period · Asian	—	1 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	3 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	4 Participants n=252 Participants • Data are being reported separately for the open-label and double-blind periods.
Race (NIH/OMB) Double-Blind Period · Native Hawaiian or Other Pacific Islander	—	2 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	0 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	2 Participants n=252 Participants • Data are being reported separately for the open-label and double-blind periods.
Race (NIH/OMB) Double-Blind Period · Black or African American	—	5 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	4 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	9 Participants n=252 Participants • Data are being reported separately for the open-label and double-blind periods.
Race (NIH/OMB) Double-Blind Period · White	—	118 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	118 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	236 Participants n=252 Participants • Data are being reported separately for the open-label and double-blind periods.
Race (NIH/OMB) Double-Blind Period · More than one race	—	0 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	0 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	0 Participants n=252 Participants • Data are being reported separately for the open-label and double-blind periods.
Race (NIH/OMB) Double-Blind Period · Unknown or Not Reported	—	0 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	0 Participants n=126 Participants • Data are being reported separately for the open-label and double-blind periods.	0 Participants n=252 Participants • Data are being reported separately for the open-label and double-blind periods.