A Single Dose-Escalation Study to Evaluate the Safety and Pharmacokinetics of Orally Administered DAA-I in Healthy Subjects (DAA-I)

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

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Placebo; Drug: DAA-I

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DAA-I 6mg; Subjects given solid compound in vials containing 6mg per vial	Drug: DAA-I
Experimental: DAA-I 50mg; Subjects given solid compound in vials containing 50mg per vial	Drug: DAA-I
Experimental: DAA-I 110mg; Subjects given solid compound in vials containing 110mg per vial	Drug: DAA-I
Placebo Comparator: Placebo; Subjects given 25ml placebo dissolved in 200ml water	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the safety and dose range of DAA-I after single oral dose administration	Evaluate the safety (in terms of effect on normal blood pressure, pulse, and 12-lead ECG) of DAA-I following a single oral administration in 12 healthy subjects (0.08 mg/kg/subject in 4 subjects, 0.7 mg/kg/subject in 4 subjects, and 1.5 mg/kg/subject in 4 subjects).	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the pharmacokinetics of DAA-I after single oral dose administrations	Evaluate the plasma level of DAA-I in each subject at baseline (0 hr) and at 0.25, 0.5, 1, 2, 3, 4, 5, 6, and 12 hr after oral administration of a single-dose of DAA-I, and determine the area under the plasma concentration versus time curve (AUC).	24 hours

Collaborators and Investigators

• Sponsor: National University Hospital, Singapore

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: December 14, 2015
• First Submitted That Met QC Criteria: January 24, 2016
• First Posted (Estimate): January 28, 2016

Study Record Updates

• Last Update Posted (Estimate): January 28, 2016
• Last Update Submitted That Met QC Criteria: January 24, 2016
• Last Verified: January 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: DAA-I

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO