Trial record 22 of 136 for:    ADHD | Open Studies | United States | Child, Adult

Study of the What the Body Does to the Drug in Subjects With Mild, Moderate, and Severe Liver Dysfunction

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by Sunovion
Sponsor:
Information provided by (Responsible Party):
Sunovion
ClinicalTrials.gov Identifier:
NCT02795637
First received: May 23, 2016
Last updated: July 11, 2016
Last verified: July 2016
  Purpose
Study of the what the body does to the drug in subjects with mild, moderate, and sever liver dysfunction (not working properly)

Condition Intervention Phase
Attention Deficit Hyperactivity Disorder (ADHD)
Binge-Eating Disorder Disorder
Drug: dasotraline
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetics of Orally Administered Dasotraline in Subjects With Mild, Moderate, and Severe Hepatic Dysfunction

Resource links provided by NLM:


Further study details as provided by Sunovion:

Primary Outcome Measures:
  • Plasma PK parameters: Area under the plasma/serum concentration-time curve from time zero to infinity (AUC0 inf) [ Time Frame: Day 1 -28 ] [ Designated as safety issue: No ]
    Plasma PK parameters: Area under the plasma/serum concentration-time curve from time zero to infinity (AUC0 inf)

  • Plasma PK parameters: time of occurrence of Cmax [ Time Frame: Day 1 -28 ] [ Designated as safety issue: No ]
    Plasma PK parameters: time of occurrence of Cmax


Secondary Outcome Measures:
  • Urine PK parameters: amount excreted in urine from time zero to time t (AEx0 t) [ Time Frame: Day 1 -28 ] [ Designated as safety issue: No ]
    Urine PK parameters: amount excreted in urine from time zero to time t (AEx0 t)

  • Urine PK parameters: renal clearance (CLR) [ Time Frame: Day 1 -28 ] [ Designated as safety issue: No ]
    Urine PK parameters: renal clearance (CLR)

  • Urine PK parameters: percent of dose excreted in urine (%fe) [ Time Frame: Day 1 -28 ] [ Designated as safety issue: No ]
    Urine PK parameters: percent of dose excreted in urine (%fe)

  • Unbound fraction of dasotraline in plasma at 10, 12, and 24 hours postdose . [ Time Frame: 0-24 hours ] [ Designated as safety issue: No ]
    Unbound fraction of dasotraline in plasma at 10, 12, and 24 hours postdose .

  • Incidence of adverse events (AEs), SAEs, and AEs resulting in study discontinuation. [ Time Frame: Day 1 -28 ] [ Designated as safety issue: Yes ]
    Incidence of adverse events (AEs), SAEs, and AEs resulting in study discontinuation.

  • Absolute values and changes from baseline in clinical laboratory tests (hematology, serum chemistry, urinalysis, prothrombin time), vital signs (respiratory rate, body temperature, supine blood pressure, and supine pulse rate), and 12 lead ECGs. [ Time Frame: Day 1 to 28 ] [ Designated as safety issue: Yes ]
    Absolute values and changes from baseline in clinical laboratory tests (hematology, serum chemistry, urinalysis, prothrombin time), vital signs (respiratory rate, body temperature, supine blood pressure, and supine pulse rate), and 12 lead ECGs.

  • Frequency of subjects with suicidal ideation or suicidal behavior using the Columbia Suicide Severity Rating Scale (C SSRS). [ Time Frame: Day 1 to 28 ] [ Designated as safety issue: Yes ]
    Frequency of subjects with suicidal ideation or suicidal behavior using the Columbia Suicide Severity Rating Scale (C SSRS).

  • Plasma PK parameters: AUC0-last, area under the blood concentration time curve from time zero to 24 hours postdose (AUC0-24) [ Time Frame: Day 1 - 28 ] [ Designated as safety issue: No ]
    Plasma PK parameters: AUC0-last, area under the blood concentration time curve from time zero to 24 hours postdose (AUC0-24)

  • Plasma PK parameters: t1/2 [ Time Frame: Day 1 - 28 ] [ Designated as safety issue: No ]
    Plasma PK parameters: t1/2

  • Plasma PK parameters: lag time (tlag) [ Time Frame: Day 1 - 28 ] [ Designated as safety issue: No ]
    Plasma PK parameters: lag time (tlag)

  • Plasma PK parameters: time of occurrence of Cmax (tmax) [ Time Frame: Day 1 -28 ] [ Designated as safety issue: No ]
    Plasma PK parameters: time of occurrence of Cmax (tmax)

  • Plasma PK parameters: apparent clearance (CL/F) [ Time Frame: Day 1 - 28 ] [ Designated as safety issue: No ]
    Plasma PK parameters: apparent clearance (CL/F)

  • Plasma PK parameters: apparent volume of distribution (Vz/F) [ Time Frame: Day 1 - 28 ] [ Designated as safety issue: No ]
    Plasma PK parameters: apparent volume of distribution (Vz/F)


Estimated Enrollment: 40
Study Start Date: May 2016
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: dasotraline
dasotraline 8mg capsule/day
Drug: dasotraline
dasotraline 8mg capsule/day
Other Name: SEP225289

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Subjects with non-impaired hepatic function must meet all of the following criteria:

  1. Male or nonpregnant, nonlactating female between 18 and 70 years of age.
  2. Subject must have a normal neurologic exam including tests for impending hepatic encephalopathy.
  3. Subject's weight is at least 50 kg.
  4. Subject's body mass index (BMI) is at least 18 kg/m2 but no more than 37 kg/m2
  5. Subject must be in general good health be demographically comparable to a least 1 subject with hepatic impairment who completed the study.
  6. Subject has a negative urine drug screen (UDS).

Subjects with hepatic impairment must meet all of the following criteria:

  1. Male or nonpregnant, nonlactating female between 18 and 70 years of age.
  2. Subject must have a normal neurologic exam including tests for impending hepatic encephalopathy. Note: Subjects with grade 0 or 1 hepatic encephalopathy will be considered for enrollment in the study.
  3. Subject's weight is at least 50 kg.
  4. Subject's BMI is at least 18 kg/m2 but no more than 37 kg/
  5. Subject has a negative UDS.
  6. Subject with stable, chronic medical conditions (eg, hypertension and hyperlipidemia) in addition to hepatic impairment that, in the opinion of the investigator, will not significantly alter the disposition of the study drug, will not place the subject at increased risk by participating in the study, and will not interfere with interpretation of the data may be permitted to enroll in the study after discussion and agreement between the investigator and medical monitor.
  7. Subject exhibits vital signs within the reference range for their age and level of hepatic impairment; subjects with vital signs outside the reference ranges may be eligible for the study if the investigator and medical monitor agree that the results are not clinically significant based on the age and hepatic impairment status of the subject, and will not impact study conduct.
  8. Subject with out-of-range laboratory results that are related to the subject's underlying condition are eligible; however, the results will need to be carefully reviewed by the investigator and medical monitor to determine if a subject is eligible for study participation. Out of range results could indicate a stable or unstable situation. If the subject is unstable (eg, rapidly changing liver tests, significantly worsened anemia compared to earlier labs, etc), then such subject would be excluded from study participation. Serum bilirubin, albumin, and prothrombin time will be assessed individually for a point score according to the Child-Pugh classification.
  9. Subject has a diagnosis of chronic hepatic impairment for at least 6 months and, in the opinion of the investigator, the severity of the subject's hepatic disease is stable, which is defined as having no clinically significant change in disease status within the 90 days prior to study drug administration, as documented by the subject's recent medical history. Copies of documentation of any clinical information used to make a previous diagnosis of hepatic dysfunction must be available. This may include abnormal liver function tests, clinical evidence of portal hypertension, a positive liver biopsy (eg, for cirrhotic disease, portal hypertension), and/or hepatic ultrasound.
  10. The total score of the Child Pugh classification must be 5 or 6 for subjects with mild hepatic dysfunction, and between 7 and 9, inclusive, for subjects with moderate dysfunction, and between 10 and 12, inclusive, for subjects with severe hepatic dysfunction.
  11. Subject receiving medication for underlying disease states or medical conditions related to hepatic dysfunction must be on a stable dose of medication and/or treatment regimen. Subjects who are receiving a fluctuating treatment regimen may be considered for inclusion if, in the opinion of the investigator, the underlying disease is under control; however these subjects must have medical monitor approval.
  12. Subject with a history of hepatic impairment due to hepatitis B is eligible provided there is no evidence of an active disease state, defined as a positive hepatitis B antigen test at screening.
  13. Subject with a history of alcohol abuse is eligible provided the urine alcohol test is negative.
  14. Subject with a history of type 2 diabetes mellitus is eligible provided that, in the investigator's opinion, he or she has stable diabetes.

Exclusion Criteria:

Any subject with non-impaired hepatic function meeting any of the following criteria will be excluded:

  1. Subject who does not tolerate venipuncture or has poor venous access that would cause difficulty for collecting blood samples.
  2. Subject has any clinically significant unstable medical abnormality, chronic disease, or history of clinically significant abnormality of the cardiovascular, respiratory, hepatic or renal systems.
  3. Subject has any clinically significant abnormal medical history, physical examination, ECG, or laboratory results.
  4. Subject has estimated creatinine clearance ≤ 60 mL/min according to the Cockcroft Gault equation.
  5. Subject has had an acute illness within 30 days prior to administration of study drug.
  6. Subject who, within 14 days prior to administration of study drug, has had a febrile illness.
  7. Subject has a disorder or history of a condition that may interfere with drug absorption, distribution, metabolism or excretion including clinically significant abnormality of the hepatic or renal system, a history of malabsorption, or previous gastrointestinal surgery that could affect drug absorption or metabolism.
  8. Subject has a presence or history of any medically diagnosed, clinically significant psychiatric disorder (including intellectual disability and substance-related disorders).
  9. Subject answers "yes" to "Suicidal Ideation" Items 4 or 5 on the C SSRS. Subjects who have significant findings for suicidal ideation upon completion of the C SSRS must be referred to the investigator for follow-up evaluation.
  10. Female subject who is pregnant, lactating, or within 6 months postpartum.
  11. Subject tests positive at screening for the hepatitis B surface antigen or hepatitis C antibody or human immunodeficiency virus (HIV 1 or HIV 2) antibody.
  12. Subject has a positive urine alcohol test.
  13. Subject has history of substance-related disorder or alcohol related disorder as defined by Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM 5) criteria within 1 year prior to screening.
  14. Subject has an average weekly alcohol intake that exceeds 21 units per week (males up to age 65) and 14 units per week (males over age 65 and females). 1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits.
  15. Subject is unwilling to stop alcohol consumption for at least 4 hours prior to admission on Day -1 (as confirmed by breath or urine alcohol test) through Day 7.
  16. Subject who has previously received dasotraline.
  17. Subject has history of intolerance to stimulants.
  18. Subject has history of allergic reaction or has a known or suspected sensitivity to any substance that is contained in the study drug formulation.
  19. Subject has had significant blood loss (> 500 mL) or donated blood, plasma, or other blood products within 30 days prior to administration of study drug.
  20. Subject has used any drugs known or suspected to affect hepatic or renal clearance capacity within 30 days prior to administration of study drug.
  21. Subject has taken any prescription or over-the-counter (OTC) medications, herbal tea, energy drinks, herbal products (eg, St John's Wort, milk thistle, etc) or supplement/supra-therapeutic doses of vitamins within 5 half lives or 14 days (whichever is longer) prior to administration of study drug or is anticipated to need any medication during the study, with the exception of those permitted by the protocol or approved by the investigator and medical monitor.
  22. Subject has taken any investigational drug within 30 days or 5 half lives (whichever is longer) prior to administration of study drug.
  23. Subject is currently a heavy user of nicotine, ie, smoking more than 20 cigarettes (eg, 1 pack) per day or equivalent (eg, e-vapor cigarette, pipe, cigar, chewing tobacco, nicotine patch or nicotine gum).
  24. Subject cannot comply with the smoking restrictions of the study site during the confinement period or is unable or unwilling to refrain from smoking and tobacco use for 2 hours prior to study drug administration and 4 hours following administration.
  25. Subject with history or suspicion of barbiturate, amphetamine, or narcotic abuse and/or positive screening results for any of these substances. Subjects who are currently receiving prescription narcotic pain relievers may be included at the investigator's and medical monitor's discretion.
  26. Subject who received anticoagulant therapy within 90 days prior to administration of study drug.

27 Subject who received live vaccine(s) within 1 month prior to screening, or intends to during the study. Note: Influenza vaccine will be allowed, if administered > 21 days prior to study drug administration.

28. Subject has used a strong inhibitor or inducer of cytochrome P450 enzymes within 30 days prior to admission.

Please see additional eligibility criteria in the Study Description section, under Detailed Description

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02795637

Contacts
Contact: CNS Medical Director 1-866-503-6351 ClinicalTrialDisclosure@sunovion.com

Locations
United States, Florida
Clinical Pharmacology of Miami, Inc. Recruiting
Miami, Florida, United States, 33014-3616
Contact: Kenneth Lasseter    305-817-2900    klasseter@clinpharmmiami.com   
Orlando Clinical Research Center Recruiting
Orlando, Florida, United States, 32809
Contact: Thomas Marbury    407-240-7878    tmarbury@ocrc.net   
United States, Georgia
Atlanta Center for Medical Research Recruiting
Atlanta, Georgia, United States, 30331
Contact: Robert Riesenberg    404-881-5800      
United States, Minnesota
DaVita Clinical Research Recruiting
Minneapolis, Minnesota, United States, 55404
Contact: Jolene Berg    612-852-7025    jolene.berg@davita.com   
United States, Texas
American Research Cororation (ARC), Texas Liver Instituete (TLI) Recruiting
San Antonio, Texas, United States, 78215
Contact: Eric Lawitz    210-256-3426    elawitz@txliver.com   
Sponsors and Collaborators
Sunovion
Investigators
Study Director: CNS Medical Director Sunovion
  More Information

Responsible Party: Sunovion
ClinicalTrials.gov Identifier: NCT02795637     History of Changes
Other Study ID Numbers: SEP360-103 
Study First Received: May 23, 2016
Last Updated: July 11, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Sunovion:
Attention deficit hyperactivity disorder (ADHD),
Binge-Eating Disorder (BED)

Additional relevant MeSH terms:
Attention Deficit Disorder with Hyperactivity
Attention Deficit and Disruptive Behavior Disorders
Hyperkinesis
Feeding and Eating Disorders
Bulimia
Binge-Eating Disorder
Disease
Neurodevelopmental Disorders
Mental Disorders
Dyskinesias
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Hyperphagia
Signs and Symptoms, Digestive
Pathologic Processes

ClinicalTrials.gov processed this record on August 28, 2016