Attention Deficit Hyperactivity DisorderPhase 2ADD201NCT00983814
Study of Droxidopa Treatment in Adults With Attention Deficit Hyperactivity Disorder With Co-administration of Carbidopa
A Phase 2 study testing Droxidopa+Carbidopa in people with Attention Deficit Hyperactivity Disorder, run by Chelsea Therapeutics at 1 site in United States.
Trial summary
Attention Deficit Hyperactivity Disorder (ADHD) is a neurobiological disorder characterized by lifelong issues of inattention, distraction, organizational difficulties, forgetfulness, restlessness, talking out of turn, difficulty waiting and interrupting others. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Attention Deficit Hyperactivity Disorder
- What is being tested?
- Droxidopa+Carbidopa
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to Jul 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- At the time of consent, are between the ages of 18-55, inclusive.
- Meet DSM-IV criteria for ADHD as assessed by the Adult ADHD Clinician Diagnostic Scale (ACDS) v1.2.
- Concomitant Axis I diagnoses that are allowed include social anxiety disorder or dysthymia which does not require treatment. Psychiatric co-morbidities will be diagnosed with the Structured Clinical Interview for DSM-IV Axis Disorders (SCID).
- Must have a satisfactory medical assessment with no clinically significant abnormalities as determined by medical history, physical exam, electrocardiogram (ECG), and clinical laboratory testing.
- Must be able to swallow capsules.
- In the opinion of the investigator, the participant must understand and be able, willing and likely to fully comply with the study procedures and restrictions.
- Must have given signed and dated informed consent in accordance with Good Clinical Practice (GCP) Guidelines.
Who cannot join
- Lifetime or present history of bipolar or psychotic disorders, that in the investigator's opinion, interfere with the diagnosis and/or with the conduct of the study.
- Uncontrolled comorbid major depressive disorder, anxiety disorder or dysthymia.
- Women of childbearing potential who are not using a medically accepted contraception.
- Sexually active males whose partner is a woman of child-bearing potential must agree to use condoms for the duration of the study and for 4 weeks after the last dose.
- Women who are pregnant, breast feeding, or plan to become pregnant during the course of this study.
- Clinically significant electrocardiogram or laboratory abnormalities at screening that are deemed exclusionary in the opinion of the Principal Investigator.
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- Participants taking any psychotropic medication on a regular basis. Participants will need to be free of all psychotropic medications (one week for psychostimulants, four weeks for all other medications), except for as needed (PRN) benzodiazepines or hypnotics. Allowed psychiatric co-morbidities include social anxiety disorder or dysthymia which does not require treatment.
- Participants with any concurrent chronic or acute illness or unstable medical condition that could, in the opinion of the study physician, confound the results of safety assessments, increase risk to the participant or lead to difficulty complying with the protocol. Participants who have a history of mental retardation or severe learning disability will be excluded.
- Participants who in the investigator's opinion meet any of the exclusionary criteria specified on the FDA label of either Droxidopa or carbidopa.
- Have uncontrolled hypertension, defined as systolic blood pressure >140 millimeters of mercury (mmHg) and/or diastolic blood pressure >110 mmHg or use of ≥2 antihypertensive medications.
- Known or suspected hypersensitivity to the study medication or any of its ingredients.
- Have in the investigator's opinion any significant cardiac arrhythmia.
- Any significant systemic, hepatic, cardiac or renal illness.
- Diabetes mellitus or insipidus.
- Have a history of closed angle glaucoma.
- Have a known or suspected current malignancy. Participants with a history of cancer must be symptom- and treatment-free for at least 5 years prior to randomization, with the exception of participants with non-melanoma, non-invasive skin cancers (such as basal cell carcinoma), who should not have had an intervention or recurrence within one year of starting the study.
- Participants with known gastrointestinal illness or other gastrointestinal disorder that may, in the investigator's opinion, affect the absorption of study drug.
- In the investigator's opinion, have clinically significant abnormalities on clinical examination or laboratory testing.
- In the investigator's opinion, are unable to adequately co-operate because of individual or family situation.
- Are not able or willing to comply with the study requirements for the duration of the study.
- Have participated in another clinical trial with an investigational agent (including named participant or compassionate use protocol) within 1 month before the start of the study.
- Previous enrollment in the study.
Trial locations and contacts
1 site in 1 country.
United States1 site
VA New York Harbor Healthcare System/New York University Langone Medical Center
New York, New York, 10010
About this study
Official title: A Two-Period Trial (Open-Label and Randomized Placebo-Controlled Substitution) of Droxidopa Treatment in Adults With ADHD With Co-administration of Carbidopa
Attention Deficit Hyperactivity Disorder (ADHD) is a neurobiological disorder characterized by lifelong issues of inattention, distraction, organizational difficulties, forgetfulness, restlessness, talking out of turn, difficulty waiting and interrupting others. ADHD is the second most common neuropsychiatric disorder affecting 4.4% of the United States (US) adult population, or between 8-9 million individuals.
Droxidopa (L-dihydroxyphenylserine (L-DOPS)) is a synthetic catecholamine which is converted to norepinephrine (NE) via decarboxylation, resulting in increased levels of NE centrally in the central nervous system (CNS) and peripherally. Co-treatment with carboxylase inhibitors, such as carbidopa, given with droxidopa, can increase the CNS levels of NE with greater crossing of the blood-brain barrier. Droxidopa has received orphan drug approval by the Food and Drug Administration (FDA) for the treatment of symptomatic neurogenic orthostatic hypotension in individuals with primary autonomic failure. The half-life of droxidopa is approximately 2-3 hours, resulting in administration three times daily.
Read the detailed description
This will be a 12-week study of twenty enrolled participants with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) criteria adult ADHD (age 18-55), with a goal of completing twenty participants in the trial. The primary objective of this study is to determine the effect of droxidopa therapy on adult ADHD symptoms over the course of a six-week open-label titration period followed by a two-week double-blind, placebo-controlled period. The primary outcome measure will be changes from baseline in total score on the Adult ADHD Investigator Symptom Rating Scale (AISRS). Secondary measures will be changes in self-reported ADHD symptoms on the Adult ADHD Self-Report Scale (ASRS v1.1) and global impairment on the Clinician Global Impression Scale (CGI).
- Conditions
- Attention Deficit Hyperactivity Disorder
- Being tested
- Droxidopa+Carbidopa
- Keywords
- Attention Deficit Hyperactivity Disorder, ADHD, Adult ADHD, Adult Attention Deficit Hyperactivity Disorder
- Medical subject headings
- Attention Deficit Disorder with Hyperactivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Droxidopa+CarbidopaDrug
Also called Droxidopa, L-threo-dihydroxyphenylserine, L-DOPS
3 weeks of open label droxidopa (L-dihydroxyphenylserine (L-DOPS)) (200, 400, or 600mgs TID) monotherapy followed by 3 weeks of droxidopa in combination with carbidopa (25mg or 50mg TID) followed by 2 weeks of double blind continued droxidopa+carbidopa or placebo
| Study group | Role | What they receive |
|---|---|---|
| Droxidopa+Carbidopa Open-Label | Experimental | 3 weeks of open label droxidopa (200, 400, or 600 milligrams [mg] three times daily [TID]) monotherapy followed by 3 weeks of droxidopa in combination with carbidopa (25 mg or 50 mg TID). Receives: Drug: Droxidopa+Carbidopa |
| Placebo Randomized Period | Placebo comparator | 2 week double-blind period in which participants either continued to receive droxidopa+carbidopa treatment or placebo Receives: Drug: Droxidopa+Carbidopa |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Total AISRS Score at the End of Double-blind Treatment (Week 8)
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.
Measured: Baseline, Week 8
Secondary outcomes (2)
Change From Baseline in Adult ADHD Self-Report Scale (ASRS) v1.1 Total Score at the End of Double-blind Treatment (Week 8)
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.
Measured: Baseline, Week 8
Change From Baseline in Global Impairment on the Clinician Global Impression (CGI) Scale at the End of Double-blind Treatment (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.
Measured: Baseline, Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2009 (estimated)
- Study startOct 2009
- Primary completionMay 2011
- Study completionJul 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Attention Deficit Hyperactivity DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chelsea Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lenard A Adler, M.D., Principal investigator, VA New York Harbor Healthcare System/New York University Langone Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00983814
- Sponsor's protocol ID
- Droxidopa ADD201
- Acronym
- ADD201
- Status last verified
- Mar 2024
- First submitted
- 23 Sep 2009
- Last updated
- 18 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Kessler RC, Adler L, Barkley R, Biederman J, Conners CK, Demler O, Faraone SV, Greenhill LL, Howes MJ, Secnik K, Spencer T, Ustun TB, Walters EE, Zaslavsky AM. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry. 2006 Apr;163(4):716-23. doi: 10.1176/ajp.2006.163.4.716.
PubMed 16585449Adler LA, Gorny SW. Pilot Study of Droxidopa With Carbidopa in Adults With ADHD. J Atten Disord. 2019 Jan;23(2):189-198. doi: 10.1177/1087054715580393. Epub 2015 Apr 23.
PubMed 25907673
Study at a glance
From the registry record, last updated by the sponsor on 18 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Two-Period Trial (Open-Label and Randomized Placebo-Controlled Substitution) of Droxidopa Treatment in Adults With ADHD With Co-administration of Carbidopa
- ClinicalTrials.gov ID
- NCT00983814
- Acronym / sponsor ID
- ADD201 / Droxidopa ADD201
- Conditions
- Attention Deficit Hyperactivity Disorder
- Keywords
- Attention Deficit Hyperactivity Disorder, ADHD, Adult ADHD, Adult Attention Deficit Hyperactivity Disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Chelsea TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Oct 2009
- Primary completion
- May 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 24 Sep 2009 (estimated)
- Results
- Posted 18 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Attention Deficit Hyperactivity Disorder (ADHD) is a neurobiological disorder characterized by lifelong issues of inattention, distraction, organizational difficulties, forgetfulness, restlessness, talking out of turn, difficulty waiting and interrupting others. ADHD is the second most common neuropsychiatric disorder affecting 4.4% of the United States (US) adult population, or between 8-9 million individuals.
Droxidopa (L-dihydroxyphenylserine (L-DOPS)) is a synthetic catecholamine which is converted to norepinephrine (NE) via decarboxylation, resulting in increased levels of NE centrally in the central nervous system (CNS) and peripherally. Co-treatment with carboxylase inhibitors, such as carbidopa, given with droxidopa, can increase the CNS levels of NE with greater crossing of the blood-brain barrier. Droxidopa has received orphan drug approval by the Food and Drug Administration (FDA) for the treatment of symptomatic neurogenic orthostatic hypotension in individuals with primary autonomic failure. The half-life of droxidopa is approximately 2-3 hours, resulting in administration three times daily.
Detailed description
This will be a 12-week study of twenty enrolled participants with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV) criteria adult ADHD (age 18-55), with a goal of completing twenty participants in the trial. The primary objective of this study is to determine the effect of droxidopa therapy on adult ADHD symptoms over the course of a six-week open-label titration period followed by a two-week double-blind, placebo-controlled period. The primary outcome measure will be changes from baseline in total score on the Adult ADHD Investigator Symptom Rating Scale (AISRS). Secondary measures will be changes in self-reported ADHD symptoms on the Adult ADHD Self-Report Scale (ASRS v1.1) and global impairment on the Clinician Global Impression Scale (CGI).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Droxidopa+Carbidopa Open-Label | Experimental | Drug: Droxidopa+Carbidopa3 weeks of open label droxidopa (200, 400, or 600 milligrams [mg] three times daily [TID]) monotherapy followed by 3 weeks of droxidopa in combination with carbidopa (25 mg or 50 mg TID). |
| Placebo Randomized Period | Placebo comparator | Drug: Droxidopa+Carbidopa2 week double-blind period in which participants either continued to receive droxidopa+carbidopa treatment or placebo |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- At the time of consent, are between the ages of 18-55, inclusive.
- Meet DSM-IV criteria for ADHD as assessed by the Adult ADHD Clinician Diagnostic Scale (ACDS) v1.2.
- Concomitant Axis I diagnoses that are allowed include social anxiety disorder or dysthymia which does not require treatment. Psychiatric co-morbidities will be diagnosed with the Structured Clinical Interview for DSM-IV Axis Disorders (SCID).
- Must have a satisfactory medical assessment with no clinically significant abnormalities as determined by medical history, physical exam, electrocardiogram (ECG), and clinical laboratory testing.
- Must be able to swallow capsules.
Key exclusion criteria (22 listed)
- Lifetime or present history of bipolar or psychotic disorders, that in the investigator's opinion, interfere with the diagnosis and/or with the conduct of the study.
- Uncontrolled comorbid major depressive disorder, anxiety disorder or dysthymia.
- Women of childbearing potential who are not using a medically accepted contraception.
- Sexually active males whose partner is a woman of child-bearing potential must agree to use condoms for the duration of the study and for 4 weeks after the last dose.
- Women who are pregnant, breast feeding, or plan to become pregnant during the course of this study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Droxidopa+CarbidopaAlso: Droxidopa, L-threo-dihydroxyphenylserine, L-DOPS3 weeks of open label droxidopa (L-dihydroxyphenylserine (L-DOPS)) (200, 400, or 600mgs TID) monotherapy followed by 3 weeks of droxidopa in combination with carbidopa (25mg or 50mg TID) followed by 2 weeks of double blind continued droxidopa+carbidopa or placebo | Drug | Droxidopa+Carbidopa Open-Label, Placebo Randomized Period |
Primary outcome
Change From Baseline in Total AISRS Score at the End of Double-blind Treatment (Week 8)
Time frame: Baseline, Week 8
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.
2 secondary outcomes
Change From Baseline in Adult ADHD Self-Report Scale (ASRS) v1.1 Total Score at the End of Double-blind Treatment (Week 8)
Time frame: Baseline, Week 8
Change From Baseline in Global Impairment on the Clinician Global Impression (CGI) Scale at the End of Double-blind Treatment (Week 8)
Time frame: Baseline, Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16585449Kessler RC, Adler L, Barkley R, Biederman J, Conners CK, Demler O, Faraone SV, Greenhill LL, Howes MJ, Secnik K, Spencer T, Ustun TB, Walters EE, Zaslavsky AM. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry. 2006 Apr;163(4):716-23. doi: 10.1176/ajp.2006.163.4.716.
- Derived from this study: PubMed 25907673Adler LA, Gorny SW. Pilot Study of Droxidopa With Carbidopa in Adults With ADHD. J Atten Disord. 2019 Jan;23(2):189-198. doi: 10.1177/1087054715580393. Epub 2015 Apr 23.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lenard A Adler, M.D. principal investigator
VA New York Harbor Healthcare System/New York University Langone Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Droxidopa+Carbidopa in people with Attention Deficit Hyperactivity Disorder, run by Chelsea Therapeutics at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Apr 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Total AISRS Score at the End of Double-blind Treatment (Week 8) (time frame: Baseline, Week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00983814, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Apr 2024.