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Phase I Clinical Study in Japanese Healthy Adult Males to Evaluate the Safety, Tolerability, and Pharmacokinetics of TR-012001

A Phase I Study of TR-012001 in Healthy Japanese Adult Males

21

The study was conducted in 21 healthy Japanese adult males who met all of the inclusion criteria and none of the exclusion criteria. Age (mean (SD)) was 34.2 (8.1) years, with the range from 22 to 44 years. BMI (mean (SD)) was 21.73 (1.50) kg/m^2, with the range from 18.9 to 24.2 kg/m^2.

As stated in the protocol, all (21) healthy Japanese adult male subjects, who signed the informed consent and passed the screening test, were enrolled in the study and assigned to Group A, B, or C. Study drug was administered to all 21 subjects, 19 completing the study and two discontinued. After completing the dosing of Group A, Period II, an adverse event (COVID-19) was observed in one subject, and according to the subject's symptoms and clinical examination results, the investigator decided that there was a problem continuing the study from an aspect of the subject's safety, and discontinued the study for this subject. After completing the dosing of Group B, Period I, an adverse event (COVID-19) was observed in one subject, and according to the subject's symptoms and clinical examination results, the investigator decided that there was a problem continuing the study from an aspect of the subject's safety, and discontinued the study for this subject.

In this study, no serious adverse events, including death, were observed in any treatment group. Two subjects had adverse events leading to discontinuation, both of which were "COVID-19", judged to be unrelated to the study drug, and resolved within the study period. In this study, adverse events judged to be of moderate severity were observed in 5 of 21 (23.8%) subjects. Of these, 2 subjects had adverse reactions, and resolved within 4 hours after the study drug administration. The other moderate adverse events were not related to the study drug and resolved within the study period. All other adverse events were mild in severity and all resolved within the study period.

Primary outcome measures (Safety)- In this study, adverse events were observed in 17 of 21 subjects (81.0%). Adverse events were observed ranging from 66.7% to 83.3% of subjects across the groups treated with the study drug. In addition, no serious adverse events including death were observed in any treatment group. Two subjects had adverse events leading to discontinuation, both of which were "COVID-19", judged to be unrelated to the study drug, and resolved within the study period. In this study, adverse events judged to be of moderate severity were observed in 5 of 21 (23.8%) subjects. All other adverse events were mild in severity and all resolved within the study period.

In this study, four doses of TR-012001 were administered to healthy Japanese adult males, and the safety and tolerability of TR-012001 under the condition of this study were demonstrated.

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031210658

Kanazashi Shuichi

SNLD, Ltd

8-1 Akashicho,Chuo-ku, Tokyo

snld.clinicaltrials@snbl.com

Ise Ryota

SNLD, Ltd

8-1 Akashicho,Chuo-ku, Tokyo

+81-3-5565-6148

snld.clinicaltrials@snbl.com

Complete

Mar. 04, 2022

Interventional

randomized controlled trial

open(masking not used)

uncontrolled control

parallel assignment

other

(1)Those who have been fully informed of the purpose and content of this study prior to the start of screening, and have freely and voluntarily given written consent to participate in this study.
(2)Those who are at least 20 years old and under 45 years old on the date of obtaining document consent.
(3)Body weight of 50 kg or more at screening and Body Mass Index (BMI) of 18.5 kg/m2 to 25.0 kg/m2.
(4)Patients who have been diagnosed as healthy by the investigator through a screening test and have been determined to be eligible for this study.
(5)Those who agree to use the contraceptive methods described in the contraceptive method guidance throughout the study period.

(1)Persons with angle-closure glaucoma.
(2)Persons with asthma.
(3)Patients with otolaryngological diseases or nasal findings (rhinitis, nasal discharge, nasal obstruction, epistaxis, nasal septal curvature, etc.) that may affect this study (as examined by an otolaryngologist). In particular, with regard to nasal septal curvature, if it is considered to affect this study, such as inability to insert a nasal device. At the time of screening, an olfactory test is conducted using Open Essence test kit, and as a rule, those with less than 8 correct answers out of 12 items are excluded.
(4)Persons with mental, central nervous system, cardiopulmonary, hepatic, renal, hematological, metabolic, or other diseases that may affect this study.
(5)A lifetime history of suicide attempts (including ongoing, previously interrupted or aborted attempts) or suicidal ideation within 6 months prior to screening. Assess using the C-SSRS. If there is a history of suicidal ideation, the timing of the ideation should be confirmed.
(6)Those with abnormal resting blood pressure and pulse rate (any of the following) at screening.
- Supine systolic blood pressure 140 mmHg or above or less than 90 mmHg
- Supine diastolic blood pressure 90 mmHg or above or less than 50 mmHg
- Supine pulse rate of less than 40 beats per minute or more than 100 beats per minute
- Systolic blood pressure in the standing position (after 3 minutes in the standing position) is 20 mmHg or more lower than in the supine position, or symptoms such as dizziness are present.
(7)Those with a fever (37.5 degree Celsius or higher).
(8)Patients with hemoglobin level less than 13.0 g/dL at screening.
(9)Others who have abnormal findings in blood or urine tests and who are judged by the investigator to be unsuitable as subjects for this study.
(10)Those who have abnormalities in the electrocardiogram at the time of screening and who are judged by the investigator to be unsuitable as subjects for this study.
(11)Persons who are hypersensitive or allergic to drugs used in this clinical trial, or any additive of TR-012001, or who have a history of severe allergy (e.g. anaphylaxis) to other drugs or other substances.
(12)Persons with chronic abnormal bowel movements (chronic constipation, chronic diarrhea, irritable bowel syndrome, etc.).
(13)Previous resection of the upper gastrointestinal tract (esophagus, stomach, duodenum, upper small intestine) (excluding appendicectomy).
(14)Persons who have taken drugs (prescription drugs, over-the-counter drugs, herbal medicines, dietary supplements, vitamins, etc.) within one week prior to admission (or for a longer period of time equal to five times the half-life), or who will be required to take such drugs by the end of the examination.
(15)Persons who have used nasal medications within 1 week (or 5 times the half-life, whichever is longer) prior to admission, or who need to use nasal medications by the end of the study.
(16)Smokers, or those who have quit smoking within 6 months prior to admission.
(17)Alcoholics, drug addicts, and those who are positive in urine drug abuse screening tests (as a rule, phencyclidine, benzodiazepines, cocaine, methamphetamine, marijuana, morphine narcotics, barbiturates, tricyclic antidepressants, methylenedioxymethamphetamine, oxycodone, propoxyphene) in the following tests.
(18)Those who have collected 400 mL or more of blood within 12 weeks prior to admission or 200 mL or more of blood within 4 weeks through blood donation, etc.
(19)Those who have participated in other clinical trials and received medication within 3 months prior to the administration of the study drug. However, even if the period is longer than this, those who have been judged by the investigator to be inappropriate to participate in this study in consideration of the characteristics of the previous study drug.
(20)Those who are positive for either syphilis seroreaction, HBs antigen, HCV antibody, or HIV antigen/antibody at the time of screening.
(21)Those who are positive for SARS-CoV-2 antigen test performed on each admission to the site.
(22)Others who are judged by the investigator to be unsuitable as subjects for this study.

Male

Parkinson's Disease

In groups A and B, single ascending doses of TR-012001 will be administered after a pretreatment of an enzyme inhibitor. Patients will be fasted for at least 10 hours before TR-012001 administration and 4 hours after administration.
In group C, the oral drug will be administered as a reference. Alternatively, TR-012001 will be administered with or without a pretreatment of an enzyme inhibitor. Patients should fast for at least 10 hours before the administration of oral drug and TR-012001, and fast for 4 hours after the administration.

Safety evaluation
(1)General physical examination (subjective symptoms, other findings), vital signs (temperature, blood pressure, pulse rate), laboratory tests (hematology, blood biochemistry, urinalysis), Columbia Suicide Severity Rating Scale (C-SSRS)
(2)Otolaryngological (nasal cavity scrutiny) findings: evaluation of subjective symptoms (nasal cavity discomfort, burning, itching, pain, nasal obstruction, abnormal taste, nasal discharge, sneezing); evaluation of other findings by the otolaryngologist (nasal cavity ulceration, redness, edema, rhinorrhea, bleeding)
(3)Adverse events (type, severity, seriousness, date and time of start, duration, outcome, causal relationship with the study drug, number of cases or incidence rate)

+81-3-5213-0028

Feb. 25, 2022

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