Clinical trial NCT02666196: A Single Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of Orally Administered DAA-I in Healthy Subjects
Official title: A Single Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of Orally Administered DAA-I in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: National University Hospital, Singapore
Sponsor class: OTHER
First posted: 2016-01-28
Enrollment: 18
Sex: ALL
Minimum age (years): 21
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP

Brief summary: This is a placebo-controlled randomized phase 1 study to investigate the safety and pharmacokinetics of DAA-I in a cohort of healthy subjects.

Detailed description: The study will be a single-blind, step-wise dose escalation, placebo controlled study in healthy subjects consisting of up to 3 dose steps of DAA-I. In the sequential step wise design, a single dose of DAA-I or placebo will be administered to 6 subjects for one treatment group. For each dose step, 4 subjects will receive DAA-I and 2 subjects will receive placebo. Subjects will be randomly allocated to one dose step. Step One would have to be completed before Step Two. Escalation up to Step Two and subsequent steps would depend on the safety results from the preceding step(s). There will be an interval of 6 hours between the dosing of the first and second DAA-I-treated volunteers of each cohort to allow for early cardiovascular monitoring. Only if there are no safety signals identify from these subjects as assessed by the Safety Review Committee can simultaneous dosing of the remaining volunteers be carried out.

Eligibility criteria: Inclusion Criteria:

1. Overtly healthy males or females as determined by medical history and physical examination.
2. Between the ages of 21 and 50 years, inclusive.
3. Weight limits within range of Body Mass Index (BMI) 19-30kg/m2
4. Renal, hepatic and blood chemistry results within normal range.
5. Normal blood pressure and heart rate as determined by the investigator.(Normal range: Systolic BP 100-140mmHg;Diastolic BP 40-90mmHg; Heart rate 50 - 100 beats per minute)
6. Temperature between 36oC to 37.4oC
7. Electrocardiogram considered as within normal limits by the investigator.
8. Are reliable and willing to make themselves available for the duration of the study.
9. Ability to provide informed consent.

Exclusion Criteria:

1. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, neurological disorders capable of altering the absorption, metabolism or elimination of drugs, or of constituting a risk factor when taking the study medication.
2. Evidence of significant active haematologic disease and/or blood donation in the last 3 months.
3. Are pregnant or intend to become pregnant during the course of the study.
4. Sexually active women of childbearing age not actively practising birth control by using oral contraceptives or an intrauterine device (IUD).
5. Women who are lactating.
6. History of allergic reactions to angiotensin inhibitor (AI), angiotensin II inhibitors, DAA-I or other relevant allergic reactions of any origins.
7. Participation in a study involving administration of an investigational compound within the past 30 days.

Primary outcomes:
measure: Evaluate the safety and dose range of DAA-I after single oral dose administration
timeFrame: 24 hours
Secondary outcomes:
measure: Evaluate the pharmacokinetics of DAA-I after single oral dose administrations
timeFrame: 24 hours
Other outcomes:
Locations:
Study officials:
References:
citation: Lee KO, Khoo CM, Chowbay B, Chan YH, Sim MK. A Single Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of Orally Administered Des-Aspartate Angiotensin I in Healthy Subjects. Drugs R D. 2016 Dec;16(4):317-326. doi: 10.1007/s40268-016-0143-y.