A Phase 1, Two-part, Double-blind, Placebo-controlled Study of the Safety, Tolerability and Pharmacokinetics of Single and Multiple Ascending Doses of SPR206 in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 94
- 试验地点
- 1
- 主要终点
- Treatment emergent adverse events assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion [Safety and Tolerability]
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability and pharmacokinetics of single and multiple intravenous doses of SPR206 when administered to healthy adult volunteers.
详细描述
This Phase 1 First in Human study is designed to assess the safety, tolerability, and pharmacokinetics of single and multiple intravenous doses of SPR206 when administered to healthy adult volunteers. This is a randomized, double-blind, placebo-controlled, ascending dose, multi-cohort trial. A total of 104 healthy volunteers will be enrolled in 13 cohorts. The study will be conducted in two phases: A single ascending dose (SAD) phase, followed by a multiple ascending dose (MAD) phase. In SAD, participants in Cohorts 1 - 8 will receive one dose of SPR206 or placebo. In MAD, participants in Cohorts 9 - 12 will receive multiple doses of SPR206 or placebo for 7 consecutive days, and a final cohort, Cohort 13, will receive multiple doses of SPR206 or placebo for 14 consecutive days at a dose deemed safe and tolerable and not to exceed the maximum dose administered to participants in Cohorts 9 - 12. In both parts sequential cohorts will be exposed to increasing doses of SPR206.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Subjects will be randomized in a 3:1 ratio of SPR206 to placebo.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adult males and/or females (of non-childbearing potential), 18 to 55 years of age (inclusive) at the time of screening.
- •BMI ≥ 18.5 and ≤ 29.9 (kg/m2) and weight between 55.0 and 100.0 kg (inclusive) for all cohorts;
- •Medically healthy without clinically significant abnormalities at the screening visit or Day -1, including:
- •Physical examination (PE) and vital signs including temperature, pulse, respiratory rate, and blood pressure;
- •Triplicate electrocardiograms (ECGs) taken at least 1 minute apart with QTcF interval duration less than 450 msec obtained as an average from the triplicate screening and pre-dose Day 1 ECGs after at least 5 min in a semi-supine quiet rest;
- •Hemoglobin/hematocrit, white blood cell (WBC) count, and platelet count equal to or greater than the lower limit of normal range of the reference laboratory;
- •Serum creatinine and bilirubin (total and conjugated) equal equal to or less than the upper limit of normal for the reference laboratory. Serum urea, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) equal to or less than 1.5 times the upper limit of normal for the reference laboratory; results of all other clinical chemistry and urine analytes without any clinically significant abnormality.
- •Discussion between the PI and the Medical Monitor (MM) is encouraged regarding the potential significance of any laboratory value that is outside of the normal range during the pre-dose period.
- •Be non-smokers (including tobacco, e-cigarettes, nicotine patches, or marijuana) for at least 1 month prior to participation in the study;
- •Willing and able to provide written informed consent;
- •Be willing and able to comply with all study assessments and adhere to the protocol schedule;
- •Have suitable venous access for drug administration and blood sampling;
- •If female, be of non-childbearing potential (e.g. post-menopausal as demonstrated by follicle stimulating hormone (FSH) or surgical sterilization i.e., tubal ligation or hysterectomy). Provision of documentation is not required for female sterilization, verbal confirmation is adequate;
- •If male, a willingness not to donate sperm and if engaging in sexual intercourse with a female partner who could become pregnant, a willingness to use a condom in addition to having the female partner use a highly effective method of birth control (such as an intrauterine device, diaphragm, oral contraceptives, injectable progesterone, subdermal implants, or a tubal ligation). This criterion applies to males (and/or female partners) who are surgically sterile and must be followed from the time of first study drug administration until 90 days after the final administration of study drug.
- •Are fluent in English such that they are able to understand the informed consent form written in English and do not require use of an interpreter.
排除标准
- •History or presence of significant cardiovascular, pulmonary, hepatic, renal, hematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or surgery within the past three months determined by the PI to be clinically relevant;
- •History of known or suspected Clostridium difficile infection;
- •History of seizure disorders;
- •Positive urine drug/alcohol testing at screening or check-in (Day -1);
- •Positive testing for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C antibodies (HCV);
- •History of substance abuse or alcohol abuse (defined as greater than 2 standard drinks on average each and every day, where 1 standard drink is defined as containing 10 g of alcohol and is equivalent to 1 can or stubby of mid-strength beer, 30 ml nip spirits, or 100 ml wine) within the previous 5 years;
- •Use of any prescription medication or any over-the-counter medication, herbal products, vitamins, diet aids or hormone supplements within 7 days prior to randomisation;
- •Documented hypersensitivity reaction or anaphylaxis to any medication;
- •Donation of blood or plasma within 30 days prior to randomisation, or loss of whole blood of more than 500 mL within 30 days prior to randomisation, or receipt of a blood transfusion within 1 year of study enrollment;
- •Participation in a New Chemical Entity clinical study within the previous 3 months or a marketed drug clinical study within the 30 days before the first dose of IMP. (Washout period between studies is defined as the period of time elapsed between the last dose of the previous study and the first dose of the next study);
- •Any other condition or prior therapy, which, in the opinion of the PI, would make the volunteer unsuitable for this study, including unable to cooperate fully with the requirements of the study protocol or likely to be non-compliant with any study requirements.
- •Participants in Cohort 13 should not have participated in any previous cohort of this study.
研究组 & 干预措施
SPR206
SAD Cohorts: Subjects will receive single doses of SPR206 via IV infusion over one hour. Planned doses to be studied are: 10, 25, 50, 100, 200, 300, 350 and 400mg. If the 300 mg dose is not deemed safe and well-tolerated, a dose of 250 mg will be used.
MAD Cohorts: Subjects will receive SPR206 via IV infusion over one hour q8h for 7 consecutive days (Cohorts 9 - 12) and over one hour q8h for 14 consecutive days (Cohort 13). Up to five dose groups will be studied. Planned doses will be 25 mg, 50 mg, 100 mg and 150 mg with dosing occurring q8h for 7 consecutive days (Cohorts 9 - 12) and q8h for 14 consecutive days (Cohort 13). Cohort 13 participants will be dosed at a dose deemed safe and tolerable, not to exceed the maximum dose tested in previous MAD dose cohorts.
.
干预措施: SPR206 (Drug)
Placebo
The placebo used during this study is normal saline (0.9% sodium chloride for injection).
SAD Cohorts: Subjects will receive single infusions of placebo (0.9% sodium chloride for injection) over one hour.
MAD Cohorts: Subjects will receive q8h infusions of placebo over 1 hour for 7 consecutive days (Cohorts 9 - 12) and q8h infusions of placebo over 1 hour for 14 consecutive days (Cohort 13).
干预措施: Placebo (Drug)
结局指标
主要结局
Treatment emergent adverse events assessments after single and multiple ascending dose administration at baseline and repeatedly until study completion [Safety and Tolerability]
时间窗: SAD: Up to 7 days; MAD: Up to 21 days for Cohorts 9 - 12 and up to 28 days for Cohort 13.
This outcome combines the measure of the number of subjects experiencing adverse events (AEs), the nature and severity of those AEs and their relationship to the study treatment
次要结局
- Pharmacokinetics: Area under the concentration-time curve from time 0 to infinity (AUC0-inf)(MAD: Day 7 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36 and 48 hours post infusion start.)
- Pharmacokinetics: Time to maximum concentration (Tmax)(MAD: Day 7 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36, and 48 hours post infusion start.)
- Pharmacokinetics: Maximum concentration (Cmax)(MAD: Day 7 (Cohorts 9 -12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36, and 48 hours post infusion start.)
- Pharmacokinetics: Terminal half-life (t1/2)(MAD: Day 1 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36 and 48 hours post infusion start.)
- Pharmacokinetics: Volume of distribution (Vd)(MAD: Day 7 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36 and 48 hours post infusion start.)
- Pharmacokinetics: Area under the concentration-time curve from time 0 to last measurable time-point (AUC0-t)(MAD: Day 7 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36, and 48 hours post infusion start.)
- Pharmacokinetics: Terminal Elimination Rate Constant (kel)(MAD: Day 7 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36, and 48 hours post infusion start.)
- Pharmacokinetics: Terminal clearance (CL)(MAD: Day 7 (Cohorts 9 - 12) and Day 14 (Cohort 13) at pre-dose and at 30, 60, 75, 90, 105, 120 and 150 minutes; and 3, 5, 8 and 12 hours post morning infusion start. 24, 36, and 48 hours post infusion start.)
- Pharmacokinetics: SPR206 excreted in urine in each collection interval(MAD: Urine samples collected on Day 1 pre-dose, 0-4 hours and 4-8 hours after start of first infusion. Days 14-15 (Cohort 13): 0-4 hours, 4-8 hours, 8-12 hours, 12-24 hours after start of infusion.)