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

ISRCTN	ISRCTN51638237
DOI	https://doi.org/10.1186/ISRCTN51638237
Clinical Trials Information System (CTIS)	2007-002229-59
Protocol serial number	The Sponsor (Amira) code: CL-AM103-01; PRA International (a contract research organization) code: AMA70921-070921
Sponsor	Amira Pharmaceuticals (USA)
Funder	Amira Pharmaceuticals (USA)

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

Primary study design	Interventional
Study design	Single-center, double-blind, randomized, placebo-controlled, single dose followed by multiple dose study.
Secondary study design	Randomised controlled trial
Scientific title	A phase 1, single-center, double-blind study of AM103 in healthy volunteers
Study objectives	To 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) studied	Healthy volunteers. Study is primarily relevant in asthma and allergic rhinitis.
Intervention	AM103 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 type	Other
Primary outcome measure(s)	1. 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.
Key secondary outcome measure(s)	1. 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.
Completion date	31/10/2007

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	72
Total final enrolment	86
Key inclusion criteria	1. 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 criteria	1. 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 enrolment	18/06/2007
Date of final enrolment	31/10/2007

Locations

Countries of recruitment

Netherlands

Study participating centre

Stationsweg 163

9470 AE Zuidlaren
9470 AE
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan	Not 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.