Trial Outcomes & Findings for Study of Droxidopa Treatment in Adults With Attention Deficit Hyperactivity Disorder With Co-administration of Carbidopa (NCT NCT00983814)

Last Updated: 2024-04-18

Results Overview

The AISRS is an 18-item validated investigator-administered instrument for the assessment of ADHD symptoms with an inattentive subscale (9 items) and a hyperactive-impulsive subscale (9 items). The severity of each of the items was rated on a 4-point scale (0-none, 1-mild, 2-moderate, 3-severe). The total score was the sum of the inattentive and hyperactive-impulsive subscales and ranged from 0 (none) to 54 (most severe). A higher score corresponded to a worse severity of ADHD.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

20 participants

Primary outcome timeframe

Baseline, Week 8

Results posted on

2024-04-18

Participant Flow

The study included 6 weeks of open-label and 2 weeks of double-blind treatment. A total of 20 participants were enrolled in the study. After 6 weeks of open-label treatment, participants were then randomized to either continue taking droxidopa+carbidopa or to receive placebo, for 2 weeks under double-blind conditions.

Participant milestones

Participant milestones
Measure	Droxidopa+Carbidopa: Open-Label Participants received droxidopa monotherapy (titrated from 200 milligrams \[mg\] three times daily \[TID\] up to 600 mg TID orally depending on clinical response and tolerability) for 3 weeks followed by 3 weeks of fixed dose treatment with droxidopa (at the previously determined tolerable level) in conjunction with carbidopa (titrated from 25 mg TID to 50 mg TID orally, with potential step-down to 25 mg TID, depending on tolerability).	Droxidopa+Carbidopa: Double-Blind Participants received fixed dose treatment with droxidopa in conjunction with carbidopa (both at doses determined during open-label treatment) for 2 weeks.	Placebo: Double-Blind Participants received placebo matched capsules for droxidopa and carbidopa TID orally for 2 weeks.
Open-Label (6 Weeks) STARTED	20	0	0
Open-Label (6 Weeks) Received at Least 1 Dose of Study Drug	2	0	0
Open-Label (6 Weeks) COMPLETED	13	0	0
Open-Label (6 Weeks) NOT COMPLETED	7	0	0
Double-Blind (2 Weeks) STARTED	0	6	5
Double-Blind (2 Weeks) Received at Least 1 Dose of Study Drug	0	6	5
Double-Blind (2 Weeks) COMPLETED	0	6	4
Double-Blind (2 Weeks) NOT COMPLETED	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Droxidopa+Carbidopa: Open-Label Participants received droxidopa monotherapy (titrated from 200 milligrams \[mg\] three times daily \[TID\] up to 600 mg TID orally depending on clinical response and tolerability) for 3 weeks followed by 3 weeks of fixed dose treatment with droxidopa (at the previously determined tolerable level) in conjunction with carbidopa (titrated from 25 mg TID to 50 mg TID orally, with potential step-down to 25 mg TID, depending on tolerability).	Placebo: Double-Blind Participants received placebo matched capsules for droxidopa and carbidopa TID orally for 2 weeks.
Open-Label (6 Weeks) Adverse Event	3	0
Open-Label (6 Weeks) Withdrawal by Subject	2	0
Open-Label (6 Weeks) Physician Decision	1	0
Open-Label (6 Weeks) Lost to Follow-up	1	0
Double-Blind (2 Weeks) Withdrawal by Subject	0	1

Baseline Characteristics

Study of Droxidopa Treatment in Adults With Attention Deficit Hyperactivity Disorder With Co-administration of Carbidopa

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Droxidopa+Carbidopa: Open-Label Only n=9 Participants Participants received droxidopa monotherapy (titrated from 200 mg TID up to 600 mg TID orally depending on clinical response and tolerability) for 3 weeks followed by 3 weeks of fixed dose treatment with droxidopa (at the previously determined tolerable level) in conjunction with carbidopa (titrated from 25 mg TID to 50 mg TID orally, with potential step-down to 25 mg TID, depending on tolerability).	Droxidopa+Carbidopa: Double-Blind n=6 Participants Participants received fixed dose treatment with droxidopa in conjunction with carbidopa (both at doses determined during open-label treatment) for 2 weeks.	Placebo: Double-Blind n=5 Participants Participants received placebo matched capsules for droxidopa and carbidopa TID orally for 2 weeks.	Total n=20 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	9 Participants n=5 Participants	6 Participants n=7 Participants	5 Participants n=5 Participants	20 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	32 years n=5 Participants	37 years n=7 Participants	37 years n=5 Participants	34 years n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	13 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants	13 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	4 Participants n=4 Participants
Region of Enrollment United States	9 participants n=5 Participants	6 participants n=7 Participants	5 participants n=5 Participants	20 participants n=4 Participants
Adult ADHD Investigator Symptom Report Scale (AISRS) Total Score	35 units on a scale STANDARD_DEVIATION 8.3 • n=5 Participants	35 units on a scale STANDARD_DEVIATION 7.9 • n=7 Participants	32 units on a scale STANDARD_DEVIATION 6.2 • n=5 Participants	34 units on a scale STANDARD_DEVIATION 7.5 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 8

Population: ITT population included all enrolled participants, who went through screening and met all inclusion/exclusion criteria. Missing data were imputed using the last observation carried forward (LOCF) method. Only participants who received the double-blind treatment were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Droxidopa+Carbidopa: Double-Blind n=6 Participants Participants received fixed dose treatment with droxidopa in conjunction with carbidopa (both at doses determined during open-label treatment) for 2 weeks.	Placebo: Double-Blind n=5 Participants Participants received placebo matched capsules for droxidopa and carbidopa TID orally for 2 weeks.
Change From Baseline in Total AISRS Score at the End of Double-blind Treatment (Week 8)	-17 units on a scale Standard Deviation 10.4	-17 units on a scale Standard Deviation 4.1

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: ITT population included all enrolled participants, who went through screening and met all inclusion/exclusion criteria. Missing data were imputed using the LOCF method. Only participants who received the double-blind treatment were evaluable for this outcome measure.

ASRS is a validated self-administered, instrument for the assessment of ADHD symptoms. It comprised of 18 items, which were rated by the participant on a 5-point scale (0=never, 1=rarely, 2=sometimes, 3=often, 4=very often). Total ASRS score was the sum of the ordinal response values for the 18 ASRS questions and ranged from 0 (never) to 72 (very often). A higher score corresponded to a worse severity of ADHD.

Outcome measures

Outcome measures
Measure	Droxidopa+Carbidopa: Double-Blind n=6 Participants Participants received fixed dose treatment with droxidopa in conjunction with carbidopa (both at doses determined during open-label treatment) for 2 weeks.	Placebo: Double-Blind n=5 Participants Participants received placebo matched capsules for droxidopa and carbidopa TID orally for 2 weeks.
Change From Baseline in Adult ADHD Self-Report Scale (ASRS) v1.1 Total Score at the End of Double-blind Treatment (Week 8)	-15 units on a scale Standard Deviation 5.1	-19 units on a scale Standard Deviation 8.6

SECONDARY outcome

Timeframe: Baseline, Week 8

7-point clinician-rated scale assessing global severity of ADHD ranging from Normal (1), Borderline (2), Mild (3), Moderate (4), Marked (5), Severe (6), to Extremely Severe (7) in functional impairment.

Outcome measures

Outcome measures
Measure	Droxidopa+Carbidopa: Double-Blind n=6 Participants Participants received fixed dose treatment with droxidopa in conjunction with carbidopa (both at doses determined during open-label treatment) for 2 weeks.	Placebo: Double-Blind n=5 Participants Participants received placebo matched capsules for droxidopa and carbidopa TID orally for 2 weeks.
Change From Baseline in Global Impairment on the Clinician Global Impression (CGI) Scale at the End of Double-blind Treatment (Week 8)	-1 units on a scale Standard Deviation 1.2	-1 units on a scale Standard Deviation 0.9

Adverse Events

Droxidopa+Carbidopa: Open-Label

Serious events: 0 serious events

Other events: 14 other events

Deaths: 0 deaths

Droxidopa+Carbidopa: Double-Blind

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Placebo: Double-Blind

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Droxidopa+Carbidopa: Open-Label n=20 participants at risk Participants received droxidopa monotherapy (titrated from 200 mg TID up to 600 mg TID orally depending on clinical response and tolerability) for 3 weeks followed by 3 weeks of fixed dose treatment with droxidopa (at the previously determined tolerable level) in conjunction with carbidopa (titrated from 25 mg TID to 50 mg TID orally, with potential step-down to 25 mg TID, depending on tolerability).	Droxidopa+Carbidopa: Double-Blind n=6 participants at risk Participants received fixed dose treatment with droxidopa in conjunction with carbidopa (both at doses determined during open-label treatment) for 2 weeks.	Placebo: Double-Blind n=5 participants at risk Participants received placebo matched capsules for droxidopa and carbidopa TID orally for 2 weeks.
Nervous system disorders Headache	25.0% 5/20 • Number of events 5 • Baseline up to Week 12 Safety population included all enrolled participants who received at least one dose of study drug.	16.7% 1/6 • Number of events 1 • Baseline up to Week 12 Safety population included all enrolled participants who received at least one dose of study drug.	0.00% 0/5 • Baseline up to Week 12 Safety population included all enrolled participants who received at least one dose of study drug.
Nervous system disorders Somnolence	25.0% 5/20 • Number of events 5 • Baseline up to Week 12 Safety population included all enrolled participants who received at least one dose of study drug.	0.00% 0/6 • Baseline up to Week 12 Safety population included all enrolled participants who received at least one dose of study drug.	0.00% 0/5 • Baseline up to Week 12 Safety population included all enrolled participants who received at least one dose of study drug.
Nervous system disorders Depressed Mood	10.0% 2/20 • Number of events 2 • Baseline up to Week 12 Safety population included all enrolled participants who received at least one dose of study drug.	0.00% 0/6 • Baseline up to Week 12 Safety population included all enrolled participants who received at least one dose of study drug.	0.00% 0/5 • Baseline up to Week 12 Safety population included all enrolled participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Myalgia	10.0% 2/20 • Number of events 2 • Baseline up to Week 12 Safety population included all enrolled participants who received at least one dose of study drug.	0.00% 0/6 • Baseline up to Week 12 Safety population included all enrolled participants who received at least one dose of study drug.	0.00% 0/5 • Baseline up to Week 12 Safety population included all enrolled participants who received at least one dose of study drug.
Nervous system disorders Insomnia	10.0% 2/20 • Number of events 2 • Baseline up to Week 12 Safety population included all enrolled participants who received at least one dose of study drug.	0.00% 0/6 • Baseline up to Week 12 Safety population included all enrolled participants who received at least one dose of study drug.	0.00% 0/5 • Baseline up to Week 12 Safety population included all enrolled participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	10.0% 2/20 • Number of events 2 • Baseline up to Week 12 Safety population included all enrolled participants who received at least one dose of study drug.	0.00% 0/6 • Baseline up to Week 12 Safety population included all enrolled participants who received at least one dose of study drug.	0.00% 0/5 • Baseline up to Week 12 Safety population included all enrolled participants who received at least one dose of study drug.

Additional Information

Email contact via

H. Lundbeck A/S

Phone: +4536301311

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place