Phase I Study of NC-2800

JRCT ID: jRCT2071210033

Registered date:09/06/2021

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Major depressive disorder
• Date of first enrollment: 05/07/2021
• Target sample size: 104
• Study type: Interventional

Intervention(s)

Single dose (Japanese): Double-blind, placebo-controlled 1, 3, 10, 45, 60 mg (NC-2800) will be administered at fasting, or 30 mg (NC-2800) will be administered at fasting / after meal (2-way crossover study).
Single dose (Caucasian): Double-blind, placebo-controlled 3, 10, 30 mg (NC-2800) will be administered at fasting.
Administration for 14 days (multiple dose, Japanese): Double-blind, placebo-controlled 3, 10, 20, 30 mg (NC-2800) will be administered once daily after breakfast.

Outcome(s)

Primary Outcome

Safety
1) Incidence rate of adverse events
2) Incidence rate of adverse reactions
3) Echocardiography
4) ECG (24-hour Holter ECG, monitor ECG, 12-lead ECG)
5) Electroencephalography (EEG) (Qualitative EEG)
Pharmacokinetics
1) Plasma concentrations (Unchanged drug/metabolite M1)
2) Urinary excretion (Unchanged drug/metabolite M1), excretion rate
3) Pharmacokinetic parameters (Cmax, AUC, Tmax, T1/2, etc.)

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: < 45age old
• Gender: Male

Include criteria

1) Japanese or Caucasian males
2) Aged >=20 and <45 years (at the time of informed consent)
3) BMI: >=18.5 and =<25.0 (Japanese) or >=18.5 and =<30.0 (Caucasian)
4) Subjects who are able to give written consent of their own free will

Exclude criteria

1)Subjects who have a past history of drug allergy
2)Subjects who have a present or past history of gastrointestinal, heart, liver or kidney, etc. disease that may affect the absorption, metabolism, or excretion of the drug. Particularly concerning liver function, persons who are assessed by the investigator/subinvestigator to be ineligible in consideration of the range of reference values of various laboratory tests.
3)Subjects who have a history of major surgery in the gastrointestinal tract, such as gastrectomy, gastroenterostomy, or enterectomy, that affects the absorption of drugs
4)Subjects who have a complication or past history of arrhythmia, such as ventricular tachycardia or QT prolongation, that requires treatment
5)Subjects who have a family history of ventricular tachycardia, congenital long QT syndrome, or unexplained arrhythmia
6)Subjects who have a past history of clinically significant respiratory disease or a history of respiratory surgery
7)Subjects who have a history of a diagnosis of chronic bowel movement disorder (e.g., chronic constipation requiring treatment, chronic diarrhea, or irritable bowel syndrome)
8)Subjects who have a past history of convulsive seizure or presyncope (excluding simple febrile seizure)
9)Subjects who have a past history of mental/neurological diseases
10)Subjects who have alcohol or drug dependence
11)Subjects who have nicotine dependence, use nicotine products (e.g., nicotine patch) or who smoke
12)Subjects who test positive for drug abuse with urinary drug screening
13)Subjects who have electrolyte abnormalities including hypokalemia (serum K: <3.5 mEq/L) and hypermagnesemia (serum Mg: >2.5 mg/dL)
14)Subjects who have a suicide risk (who responded "Yes" to Question 4 or 5 about "Suicidal ideation" on the Columbia Suicide Severity Rating Scale [C-SSRS] at screening)
15)Subjects who are tested positive for HBs antigen, serum reaction for syphilis, HCV antibody, or HIV antigen/antibody
16)Subjects with abnormal ECG findings or prolonged QT/QTc interval (e.g., QTc interval exceeding 450 msec by Fridericia correction method) at screening
17)Subjects who have taken supplements, grapefruit (fruit or juice) or St. John's wort within 2 weeks before the study treatment
18)Subjects who have taken any drugs within 2 weeks or 5 half-lives, whichever is longer, before the start of the study treatment
19)Subjects who have taken any drug containing opioid (e.g., antitussives such as codeine) within 4 weeks before the study treatment
20)Subjects who have taken any known cytochrome P450 system inhibitors (e.g., itraconazole, clopidogrel) or inducers (e.g., rifampicin) within 2 months before the study treatment
21)Subjects who have taken any other investigational drug within 3 months before the study treatment
22)Subjects who have received blood transfusion within 3 months, who have donated >=400 mL of whole blood within 3 months or >=200 mL of whole blood within 1 month, or who have donated blood components within 2 weeks before the study treatment
23)Subjects who are unable to practice proper contraception during the period from hospital admission to 3 months after discharge
24)Subjects who are assessed to be ineligible as study subjects by the investigator/subinvestigator
25) Subjects who have orthostatic hypotension at screening (a decrease in systolic blood pressure of >=20 mmHg or a decrease in absolute systolic blood pressure to below 90 mmHg, or a decrease in diastolic blood pressure of >=10 mmHg, within 3 minutes following a change in position from supine to upright)

The following exclusion criteria will be added for the multiple dose study.
26) Subjects who use glasses only for vision correction or use colored contact lenses
27) Subjects who have a right visual acuity (naked eye or corrected) of <0.3, or a history of ophthalmologic surgery (e.g., LASIK)
28) Subjects who have imbalanced pupil movement or pigment near the pupil, as detected on the ophthalmologic examination at screening

Related Information

• Primary Sponsor: Hayamizu Koki
• Secondary Sponsor: Japan Agency for Medical Research and Development