A Randomized, Double-Blind, Placebo-Controlled Phase I Study To Determine The Safety, Tolerability, Pharmacokinetics And Pharmacodynamics Of Single Ascending Doses Of PBL 1427 In Healthy Volunteers.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 1
- 主要终点
- 1.To determine safety and tolerability of PBL 1427
研究概览
简要总结
A total of 48 healthy male subjects will be enrolled in six cohorts. (Two additional subjects will be included in each cohort and will be housed till dosing to handle any withdrawn or drop out before dosing). The study will consist of six dose groups of eight subjects each in which six subjects will receive a single dose of active treatment and two subjects will receive placebo as a single dose. Subjects will be dosed in subsequent dose levels only after safety evaluation of subjects recruited in the previous dose level. The post-study period (follow-up) will be done on Day 5-9 post dose.
The subjects will undergo a screening procedure that will be valid for a period of 10 days prior to the day of admission. The subjects will be confined to the unit, approximately 10.5 hours before drug administration and until 48 h post-dose.
As per the randomization schedule, capsule(s) of A or B will be administered to each subject with 240 mL of water at ambient temperature. Subjects will be instructed not to chew or crush the capsule(s) but to consume it as a whole. Compliance for dosing will be assessed by a thorough check of the oral cavity immediately after dosing. Administration of investigational products will be carried out while the subjects are in sitting posture and they will be instructed to remain seated for two hours after dosing except when clinically indicated to change the posture or in case of any natural exigency. Thereafter, the subjects will be allowed to engage in normal activities while avoiding severe physical exertion.xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" /
The following treatments in the below cohorts will be followed as given below:
Cohort 1: A single oral dose of 20 mg of PBL 1427 (n=6) or placebo (n=2)
Cohort 2: A single oral dose of 40 mg (20 mg X 2 capsules) of PBL 1427 (n=6) or placebo (n=2)
Cohort 3: A single oral dose of 80 mg (20 mg X 4 capsules) of PBL 1427 (n=6) or placebo (n=2)
Cohort 4: A single oral dose of 150 mg of PBL 1427 (n=6) or placebo (n=2)
Cohort 5: A single oral dose of 300 mg (150 mg X 2 capsules) of PBL 1427 (n=6) or placebo (n=2)
Cohort 6: A single oral dose of 600 mg (150 mg X 4 capsules) of PBL 1427 (n=6) or placebo (n=2)
Dose levels may be modified and intermediate dose levels might be tested to determine the maximum tolerated dose (MTD)
The number of cohorts, dose levels, frequency and conditions of administration for the subsequent cohort may be altered by the Principal investigator and Sponsor after evaluation of the results of the previous group.
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 60.00 Year(s)（—）
- 性别
- Male
入选标准
- •Subjects to be enrolled in this trial must fulfil all of these criteria: •Sex: male •Age: 18-60 yr old, both inclusive •Having a Body Mass Index (BMI) between 18.5-28 kg / m2 (both inclusive) and body weight not less than 45 kg •Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; and to comply with the requirements of the entire study •Voluntarily given written informed consent to participate in this study •Be of normal health as determined by the principal investigator from medical history, physical examination and laboratory investigations, 12- lead ECG and X-ray chest of the subjects performed within 10 days prior to the admission of the study •Ability and willingness to abstain from alcohol, methylxanthine-containing beverages or food (coffee, tea, coke, chocolate, “power drinksâ€) and grapefruit (juice) from 48 h prior to each admission until study completion.
排除标准
- •Subjects meeting any of these criteria will not be enrolled in the study: •Employees of FCRL or PBL •Not willing to use contraceptives (preferably condoms) during sexual activity for the period of 3 months from the date of check-in •History of hypersensitivity and / or intolerance to Dipeptidyl peptidase (DPP)-IV inhibitors or any other related compounds.
- •â€¢History of anaphylaxis to drugs or allergic reactions in general, which the Investigator considers may affect the outcome of the study.
- •â€¢Clinically abnormal ECG and Chest X-ray.
- •â€¢Physical findings: clinically relevant abnormal physical findings (including body temperature) suggesting underlying pathologies or those which could interfere with the objectives of the study.
- •â€¢Gastrointestinal disorders likely to influence drug absorption including acute gastrointestinal symptoms (e.g. nausea, vomiting, diarrhoea, heart burn), preceding one week to admission.
- •â€¢Laboratory values that are significantly different than the normal reference range and/or are deemed to be of clinical significance by the investigator • Presence of reactive disease markers of HIV 1 and II, HBsAg,, HCV or VDRL.
- •â€¢Positive for alcohol breath test and/or urine drug screen (barbiturates, benzodiazepines, amphetamine, cocaine, opiates, tetra-hydro cannabinol).
- •â€¢ Any evidence of organ dysfunction or any clinically significant deviation from the normal, in physical or clinical determinations.
- •â€¢ History of Diabetes Mellitus or intake of any anti-diabetic medication •Diseases: relevant history of renal, hepatic, cardiovascular, respiratory, skin, haematological, endocrine, neurological or gastrointestinal diseases.
- •History of depression, psychosis, schizophrenia or any other severe psychiatric diseases, or epilepsy, or any other illness that may interfere with the aim of the study.
- •History of any significant illness in the 4 weeks preceding the screening •Medications: history of intake of any medications including over the counter medications (OTC) during the 4 weeks period prior to dosing with the IMP.
- •â€¢Blood donation: Subjects who, through completion of this study, would have donated and/or lost more than 300 mL of blood in the past 12 weeks Note: In case the blood loss is ≤ 200 mL; subject may be dosed 60 days after blood donation or last sample of the previous study •Regular smokers who smoke more than 10 cigarettes daily or have difficulty abstaining from smoking for the duration of each study period.
- •â€¢History of drug dependence or alcoholics.
结局指标
主要结局
1.To determine safety and tolerability of PBL 1427
时间窗: The subjects will be confined to the unit, approximately 10.5 hours before drug administration and until 48 h post-dose. Subjects will be housed from admission and prior to dosing at FCRL and will be shifted to Sunflag Hospital ICU well advance in time before dosing and will be housed there till discharge. Subsequent follow ups and all laboratory tests (at day 05 to day 09) will be carried out at FCRL screening area in all the cohorts.
2.To evaluate the pharmacokinetics (PK) of PBL 1427
时间窗: The subjects will be confined to the unit, approximately 10.5 hours before drug administration and until 48 h post-dose. Subjects will be housed from admission and prior to dosing at FCRL and will be shifted to Sunflag Hospital ICU well advance in time before dosing and will be housed there till discharge. Subsequent follow ups and all laboratory tests (at day 05 to day 09) will be carried out at FCRL screening area in all the cohorts.
次要结局
- To determine pharmacodynamic markers of PBL 1427 in the study population(The subjects will be confined to the unit, approximately 10.5 hours before drug administration and until 48 h post-dose. Subjects will be housed from admission and prior to dosing at FCRL and will be shifted to Sunflag Hospital ICU well advance in time before dosing and will be housed there till discharge. Subsequent follow ups and all laboratory tests (at day 05 to day 09) will be carried out at FCRL screening area in all the cohorts.)