Clinical trial NCT02827513: A Phase 1 Study to Investigate the Safety, Tolerance, Food Effect, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of Extended Release Formulations of Centanafadine (CTN) in Young Healthy Subjects
Official title: A Phase 1 Study to Investigate the Safety, Tolerance, Food Effect, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of Extended Release Formulations of Centanafadine (CTN) (Formerly Called EB-1020) in Young Healthy Subjects
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Adult Attention-deficit Hyperactivity Disorder (ADHD)
Keywords: Centanafadine
Adult attention-deficit hyperactivity disorder
Healthy participants
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor class: INDUSTRY
First posted: 2016-07-11
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to investigate the safety, tolerance, food effect, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple doses of extended release (XR) formulations of Centanafadine (CTN) in Young Healthy participants.

Detailed description: The study will be divided into three parts: A, B, C.

Part A: Single Dose, extended release (XR) Formulation Selection. This part of the study is a single dose, open label, four-period crossover design in a group of 16 healthy participants.

Part B: Multiple Ascending Dose. Part B has been designed to assess the effect of multiple doses of one formulation of XR CTN. This part of the study will be a double-blind, randomized, placebo-controlled design.

Part C: Food Effect. Part C has been designed to determine the effect food has on XR CTN. The XR formulation and dose administered will be selected after review of Part B data. This part will be an open-label, two-period crossover design in a group of 16 healthy participants.

Eligibility criteria: Inclusion Criteria:

1. Body weight within the normal range for height (body mass index \[BMI\] between 19-30 kg/m2 inclusive);
2. Negative serum pregnancy test at Screening and negative urine pregnancy test at Day -1 for females of child bearing potential;
3. Women of child-bearing potential must agree to use adequate; contraception prior to study entry, for the duration of study participation, and for 90 days following completion of therapy;
4. Be in general good health without clinically significant medical history;
5. Have clinical laboratory test results that are within the laboratory reference range; or if out of range are not clinically relevant and are acceptable to the Investigator and Sponsor medical representative;
6. Negative Human Immunodeficiency Virus (HIV), Hepatitis B and Hepatitis C Screening test;
7. Able and willing to give written informed consent.

Exclusion Criteria:

1. Use of any of the following medications will exclude a participant:

   * investigational compound within 30 days prior to Screening;
   * antipsychotic, anxiolytic, or sedative-hypnotic medication within 30 days prior to Screening;
   * any antidepressant medication within 30 days prior to Screening;
   * clonidine within 30 days prior to Screening;
   * cough/cold preparations containing stimulants/sympathomimetic agent within 7 days prior to Day -1;
   * norepinephrine reuptake inhibitors, such as tomoxetine (STRATTERA®) within 30 days prior to Day -1;
   * antihypertensive agents, including diuretics, are not permitted at any time prior to or during the study;
   * sedating antihistamines (as a single preparation or in combination) within 7 days prior to Day -1;
   * sympathomimetics, appetite suppressants, modafinil, methylphenidate, amphetamine and pemoline within 7 days prior to Day -1;
   * Use over the counter medications within 7 days of Investigational Product administration, with the exception of simple analgesics such as paracetamol, oral non-steroidal anti-inflammatory agents and the oral contraceptive pill (if applicable);
   * Use of any herbal preparations and melatonin is prohibited and should be discontinued prior to Day -1. The process for discontinuing use of herbal preparations and melatonin prior to Day -1 is at the discretion of the Investigator;
2. A history of, or current evidence for, suicidal ideation, based upon clinical interview and the Columbia Suicide Severity Rating Scale (C-SSRS);
3. A history of known or suspected seizures, spasms, infantile spasms, febrile convulsions, unexplained significant and recent loss of consciousness or history of significant head trauma with loss of consciousness or a family history (first degree relative) of epilepsy or seizures (fits);
4. Subject has a known history of hypertension or Subject has a supine systolic blood pressure (SBP) ≥140 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg. No more than one repeat measurement will be permitted;
5. Subject has a known history of orthostatic hypotension or has an orthostatic blood pressure (BP) drop of ≥20 mm Hg (based on the drop between supine and standing \[3 minutes\] SBP) at Screening or Day -1;

Note: The eligibility criteria list is not exhaustive.

Primary outcomes:
measure: Number of participants with treatment emergent adverse events and serious adverse events
timeFrame: Up to approximately 12 days
Secondary outcomes:
measure: Maximum observed plasma concentration (Cmax) of Centanafadine (CTN) and metabolite
timeFrame: For Part A: From Day 1 to 12; For Part B: Day 1, Day 2, Day 4, Day 5, Day 6, and Day 7; For Part C: Day 1 to 6
measure: Time to maximum plasma concentration (Tmax) of CTN and metabolite
timeFrame: For Part A: From Day 1 to 12; For Part B: Day 1, Day 2, Day 4, Day 5, Day 6, and Day 7; For Part C: Day 1 to 6
measure: Area under the plasma concentration-time curve from time zero until the last quantifiable time point (AUC0-last) of CTN and metabolite
timeFrame: For Part A: From Day 1 to 12; For Part B: Day 1, Day 2, Day 4, Day 5, Day 6, and Day 7; For Part C: Day 1 to 6
measure: Apparent termination elimination rate constant (kel) of CTN and metabolite
timeFrame: For Part A: From Day 1 to 12; For Part B: Day 1, Day 2, Day 4, Day 5, Day 6, and Day 7; For Part C: Day 1 to 6
measure: Apparent terminal elimination half-life (t1/2) of CTN and metabolite
timeFrame: For Part A: From Day 1 to 12; For Part B: Day 1, Day 2, Day 4, Day 5, Day 6, and Day 7; For Part C: Day 1 to 6
measure: last measurable plasma concentration (Clast) of CTN and metabolite
timeFrame: For Part A: From Day 1 to 12; For Part B: Day 1, Day 2, Day 4, Day 5, Day 6, and Day 7; For Part C: Day 1 to 6
measure: Area under the plasma concentration-time curve from time zero to infinity (AUC0-inf) from AUC0-last +Clast/kel of CTN and metabolite
timeFrame: For Part A: From Day 1 to 12; For Part B: Day 1, Day 2, Day 4, Day 5, Day 6, and Day 7; For Part C: Day 1 to 6
measure: Dose normalized Cmax (Cmax/Dose) of CTN and metabolite
timeFrame: For Part A: From Day 1 to 12; For Part B: Day 1, Day 2, Day 4, Day 5, Day 6, and Day 7; For Part C: Day 1 to 6
measure: Dose normalized AUC (AUC/Dose) of CTN and metabolite
timeFrame: For Part A: From Day 1 to 12; For Part B: Day 1, Day 2, Day 4, Day 5, Day 6, and Day 7; For Part C: Day 1 to 6
Other outcomes:
Locations:
city: Melbourne
country: Australia
Study officials:
References: