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

NCT00983814 | Completed Phase 2 Results

• 1 other identifier: Droxidopa ADD201
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Attention Deficit Hyperactivity Disorder

Keywords

Attention Deficit Hyperactivity Disorder; ADHD; Adult ADHD; Adult Attention Deficit Hyperactivity Disorder

Outcome Measures

Primary Outcomes (1)

• 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.

  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)

  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)

  Baseline, Week 8

Study Arms (2)

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).

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

Drug: Droxidopa+Carbidopa

Interventions

Droxidopa+Carbidopa DRUG

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

Also known as: Droxidopa, L-threo-dihydroxyphenylserine, L-DOPS

Droxidopa+Carbidopa Open-Label; Placebo Randomized Period

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• Chelsea Therapeutics: lead

Study Sites (1)

VA New York Harbor Healthcare System/New York University Langone Medical Center

New York, New York, 10010, United States

Location

Related Publications (2)

• 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.

  PMID: 16585449 BACKGROUND

• Adler 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.

  PMID: 25907673 DERIVED

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Interventions

Droxidopa

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Norepinephrine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Email contact via
• Organization: H. Lundbeck A/S

LundbeckClinicalTrials@Lundbeck.com

+4536301311

Study Officials

• Lenard A Adler, M.D.

  VA New York Harbor Healthcare System/New York University Langone Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2009
• First Posted: September 24, 2009
• Study Start: October 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: July 1, 2011
• Last Updated: April 18, 2024
• Results First Posted: April 18, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)