A Phase 1, Randomized, Placebo-Controlled, First-in-Human, Single and Multiple Ascending Dose Study Designed to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Orally Administered KT-621 in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 118
- 试验地点
- 1
- 主要终点
- Treatment-emergent potentially clinically significant abnormalities in vital signs: heart rate (beats per minute)
研究概览
简要总结
This is a first-in-human study to evaluate safety, pharmacokinetics, and pharmacodynamics of single and multiple dose levels of KT-621 in healthy male and female adult participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
盲法说明
The Sponsor is also masked to treatment allocation.
入排标准
- 年龄范围
- 19 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants aged 19 to 55 years (inclusive) at the time of consent, with a weight of at least 50 kg if male or 40 kg if female, and a body mass index (BMI) between 18.0 and 30.0 kg/m² (inclusive) at Screening.
- •Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study.
- •Participants must be willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
- •Male participants (and their partners of childbearing potential) and female participants must agree to the contraception requirements as specified in the clinical protocol.
- •Female participants may not be pregnant, lactating, or breast-feeding or plan to become pregnant (including ova donation) within 30 days of last study drug administration.
- •Female participants must have a negative result for pregnancy test at Screening and on admission to the CRU.
排除标准
- •Participants who have a clinically relevant history of respiratory, gastrointestinal (GI), renal, hepatic, hematological, lymphatic, endocrinological, neurological, cardiovascular, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, ophthalmological, or connective tissue diseases or disorders.
- •Participants who have a clinically relevant surgical history (eg, surgery of the GI tract that could interfere with the PK of the trial medication) Note: prior appendectomy or cholecystectomy is not exclusionary.
- •Participants with a history of alcohol or substance abuse within the previous 5 years.
- •Participants who have any known factor, condition, or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease.
- •Participants who test positive for alcohol and drugs of abuse at Screening and on admission to the CRU.
- •Participants who have acute GI symptoms at the time of Screening or admission to the CRU (eg, nausea, vomiting, diarrhea, heartburn).
- •Participants whose results from clinical laboratory safety tests are outside the local reference range at Screening and on admission to the CRU.
- •Participants who have previously received KT-621 in another cohort in this study.
- •Participants who have been dosed with any investigational drug or device in a clinical study within 30 days or 5 half-lives (whichever is longer) of KT-621/placebo administration.
研究组 & 干预措施
KT-621
Each participant receives either a single oral dose (SAD) or multiple oral doses (MAD) of KT-621.
干预措施: KT-621 (Drug)
Placebo
Each participant receives either a single oral dose (SAD) or multiple oral doses (MAD) of matched placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Treatment-emergent potentially clinically significant abnormalities in vital signs: heart rate (beats per minute)
时间窗: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
Treatment-emergent potentially clinically significant abnormalities in vital signs: respiratory rate (breaths per minute)
时间窗: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
Treatment-emergent potentially clinically significant abnormalities in vital signs: temperature (degrees Celsius)
时间窗: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
Incidence of adverse events
时间窗: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
Treatment-emergent potentially clinically-significant abnormalities in safety laboratory parameters: hematology
时间窗: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
Hemoglobin, Hematocrit, Erythrocytes, Mean corpuscular volume, Platelets, Leukocytes, Eosinophils, Basophils Neutrophils Lymphocytes Monocytes
Treatment-emergent potentially clinically significant abnormalities in safety laboratory parameters: serum chemistry
时间窗: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
Glucose, Blood urea nitrogen, Creatinine, Sodium, Potassium, Calcium, Chloride, Magnesium, Bicarbonate, Phosphate, Bilirubin, total and direct, Alkaline phosphatase, Aspartate transaminase (=SGOT), Alanine transaminase (=SGPT), Gamma glutamyl transferase, Total protein, Albumin, Creatine kinase, HbA1c, Lactate dehydrogenase (LDH)
Treatment-emergent potentially clinically significant abnormalities in safety laboratory parameters: coagulation
时间窗: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
Activated partial thromboplastin time, Prothrombin time, International Normalized Ratio, Fibrinogen
Treatment-emergent potentially clinically significant abnormalities in vital signs: blood pressure (mmHg)
时间窗: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
Treatment-emergent potentially clinically significant abnormalities in electrocardiogram values: QTcF (milliseconds)
时间窗: From enrollment through the safety follow-up visit on either Day 14 (SAD) or Day 38 (MAD)
次要结局
- Maximum concentration (Cmax): observed maximum concentrations derived from plasma concentration data(Day 1 (SAD); Day 1, Day 7, and Day 14 (MAD))
- Time to maximum concentration (Tmax): observed time to achieve maximum concentrations derived from plasma concentration data(Day 1 (SAD); Day 1, Day 7, and Day 14 (MAD))
- Area under the curve (AUC0-last): Area under the plasma concentration-time curve calculated using non-compartmental analysis from time zero to the last observed timepoint(Day 1 (SAD); Day 1, Day 7, and Day 14 (MAD))
- Area under the curve (AUC0-infinity): Area under the plasma concentration-time curve calculated using non-compartmental analysis from time zero to infinite time(Day 1 (SAD))
- Area under the curve (AUC0-tau): Area under the plasma concentration-time curve calculated using non-compartmental analysis from time zero to end of the dosing interval(Day 1, Day 7, and Day 14 (MAD))
- Terminal elimination half-life (t1/2): elimination half-life calculated using non-compartmental analysis(Day 1 (SAD) and Day 14 (MAD))
- Fraction excreted: Fraction of drug excreted unchanged in urine(Day 14 (MAD))