A phase 1, single-center, double-blind study of AM103 in healthy volunteers

ISRCTN ISRCTN51638237
DOI https://doi.org/10.1186/ISRCTN51638237
EudraCT/CTIS number 2007-002229-59
Secondary identifying numbers The Sponsor (Amira) code: CL-AM103-01; PRA International (a contract research organization) code: AMA70921-070921
Submission date
08/06/2007
Registration date
09/08/2007
Last edited
29/10/2021
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Signs and Symptoms
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Sjoerd van Marle
Scientific

Stationsweg 163
9470 AE Zuidlaren
9470 AE
Netherlands

Study information

Study designSingle-center, double-blind, randomized, placebo-controlled, single dose followed by multiple dose study.
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Not specified
Study typeNot Specified
Scientific titleA phase 1, single-center, double-blind study of AM103 in healthy volunteers
Study objectivesTo assess the following:

Primary:
Safety and tolerability of single and multiple doses of AM103 following oral administration.

Secondary:
1. Pharmacokinetics (PK) of AM103 after single and multiple doses.
2. Effects of AM103 on Pharmacodynamic (PD) markers: whole blood ionophore-stimulated leukotriene LTB4 and urinary LTE4 production.
Ethics approval(s)Medical Ethical Review Committee (METC) of the BEBO foundation (Ethics Review / Bio-medical Research) (METC van de stichting BEBO) Postbus 1004, 9400 BA Assen, and Noorderstaete 20, 9402 XB Assen, the Netherlands. Approved on 22nd May 2007.
Health condition(s) or problem(s) studiedHealthy volunteers. Study is primarily relevant in asthma and allergic rhinitis.
InterventionAM103 orally or placebo
Single doses: 50, 150, 300, 600, 1000 mg
Multiple doses: Administered once daily for 11 days. The doses are: 150, 300 and 600 mg, with an additional group to be defined (after the prior doses have concluded).
Intervention typeOther
Primary outcome measure1. Adverse events
2. Physical examinations
3. Vital signs
4. ECGs
5. Clinical laboratory values

Single Dose Study: Physical examination, vital signs, ECG, and clinical laboratory tests will be carried out on Day 4 (72 ± 4 hours, end-of study time point) after study drug administration.

Multiple Dose Study:

Vital signs will be assessed at the following timepoints:
Day 1: pre-dose, 1, 2, 4, 12, and 24 hours after study drug administration
Days 2-10: pre-dose, 2 and 12 hours after study drug administration
Day 11: pre-dose, 2, 12 and 24 hours after study drug administration

Physical examination, vital signs, ECG, and clinical laboratory tests will be carried out on Day 14 (72 ± 4 hours after the Day 11 dose).

ECGs will be carried out at the following timepoints:
Single Dose Phase: 2-4 hours after the study drug administration
Multiple Dose Phase: 2-4 hours after the first dose of study drug on Day 1 and 2-4 hours after study drug administration on Days 5 and 11.
Secondary outcome measures1. Pharmacokinetics: Concentrations of AM103 in plasma samples will be determined by validated Liquid Chromatography/Mass Spectrometry (LCMS) methods.
2. Pharmacodynamics: Whole blood ionophore-stimulated leukotriene LTB4 and urinary LTE4 production to be assayed by Enzyme Linked Immunosorbent Assay (ELISA) and mass spectrometry, respectively.
Overall study start date18/06/2007
Completion date31/10/2007

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participantsUp to 72 (40 in single dose phase; 32 in multiple dose phase)
Total final enrolment86
Key inclusion criteria1. Male or female between 18 and 65 years of age (for Multiple Dose Phase, male only)
2. Female subjects must be postmenopausal, surgically sterile, or be prepared to use two methods of contraceptives during the study and for 14 days after the end of dosing
3. Non-smoker
4. Good general health as determined by medical history, and by results of physical examination, vital signs, Electrocardiogram (ECG), and clinical laboratory tests obtained within 21 days (3 weeks) prior to study drug administration
5. Able to provide written informed consent and understand and comply with the requirements of the study
Key exclusion criteria1. Prior exposure to AM103 (no subject may participate in more than one cohort)
2. History or presence of any significant organ system disease, including phenylketonuria, as assessed by medical history, physical examination and laboratory evaluation
3. 12-lead ECG with any abnormality judged by the Investigator to be clinically significant or QTc interval of >450 milliseconds
4. Presence or history of any abnormality or illness, which in the opinion of the Investigator may affect absorption, distribution, metabolism or elimination of the study drug
5. Any screening laboratory evaluation outside the laboratory reference range that is judged by the Investigator to be clinically significant
6. Hemoglobin <7 mmol/L
7. Positive serum test for HIV, hepatitis C or hepatitis B virus infection
8. History of significant allergy to any medication
9. History of alcohol or drug abuse within the past 24 months or positive urine drug screen during screening
10. Use of any tobacco or nicotine containing product within the previous 6 months
11. Administration of any prescription drug within 21 days (oral contraceptives permitted) or over-the-counter drug (paracetamol and ibuprofen ≤1 g/day permitted) or herbal supplement within 7 days of study drug administration
12. Administration or use of any investigational drug or device within 30 days of study drug administration
13. Blood or plasma donation within 60 days prior to dosing
Date of first enrolment18/06/2007
Date of final enrolment31/10/2007

Locations

Countries of recruitment

  • Netherlands

Study participating centre

Stationsweg 163
9470 AE Zuidlaren
9470 AE
Netherlands

Sponsor information

Amira Pharmaceuticals (USA)
Industry

c/o Dr Mark Moran
9535 Waples Street, Ste. 100
San Diego
92121
United States of America

Website http://www.amirapharm.com/
ROR logo "ROR" https://ror.org/00gtmwv55

Funders

Funder type

Industry

Amira Pharmaceuticals (USA)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing planNot provided at time of registration

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article 24/02/2010 29/10/2021 Yes No

Editorial Notes

29/10/2021: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.