A Phase 1, Randomised, Double-Blind, Placebo-Controlled, First-in-Human Study of the Safety, Tolerability and Pharmacokinetics of AXN-001 in Healthy Volunteers.
- Conditions
- MigraineNeurological - Other neurological disorders
- Registration Number
- ACTRN12623000296639
- Lead Sponsor
- Avance Clinical Pty Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 36
1.Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects;
2.Adult males and females, 18 to 55 years of age (inclusive) at Screening;
3.Body mass index greater than or equal to 18.0 and less than or equal to 32.0 kg/m2, with a body weight (to 1 decimal place) greater than or equal to 50.0 kg less than or equal to 120 kg;
4.Be non-smokers (including tobacco, e-cigarettes and marijuana) for at least 3 months prior to first study drug administration and have a negative test for cotinine at the screening visit and at check-in on Day -1. Participants who smoke up to 10 cigarettes per week and have a negative cotinine test will be eligible;
5.Medically healthy without clinically significant abnormalities (in the opinion of the Investigator), including:
a.Physical examination without any clinically significant findings;
b.Systolic blood pressure in the range of 90 to 140 mmHg (inclusive) and diastolic blood pressure in the range of 40 to 90 mmHg (inclusive) after 5 minutes in supine (or semi-supine) position;
c.Heart rate in the range of 50 to 100 bpm (inclusive) after 5 minutes rest in supine (or semi-supine) position;
d.Body temperature (tympanic) in the range 35.5°C to 37.7°C (inclusive);
e.No clinically significant findings in serum chemistry, haematology, coagulation, and urinalysis tests;
f.Estimated glomerular filtration rate greater than or equal to 70mL/min/1.73m2;
g.Triplicate 12-lead ECG (taken after the volunteer has been supine (or semi-supine) for at least 5 minutes) with a QT interval corrected using the Fridericia method (QTcF) less than or equal to 450 msec for males and less than or equal to 470 msec for females and no clinically significant abnormalities;
h.Oxygen saturation (SpO2) greater than or equal to 95%.
6.Female volunteers must:
a.Be of nonchildbearing potential i.e., be surgically sterilised (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before screening) or be postmenopausal, where menopause is defined as 12 months of amenorrhea in the absence of other biological causes. Females under the age of 55 years must have a documented serum follicle-stimulating hormone (FSH) level > 40mIU/mL to confirm menopause (females who are taking Hormone Replacement Therapy (HRT) should provide evidence that they are post-menopausal or should be excluded as their post-menopausal status cannot be confirmed by measuring FSH - alternatively they would need to stop HRT to allow FSH to be measured);
b.If of childbearing potential (defined as any female who has experienced menarche and who has not undergone surgical sterilisation and is not postmenopausal), the participant:
•Must have a negative serum test at the screening visit and a negative urine pregnancy test within 24 hours prior to the start of study drug;
•Must not be breastfeeding, lactating or planning pregnancy during the study period;
•Must agree not to attempt to become pregnant;
•If not exclusively in same-sex relationships, must agree to use adequate contraception (which is defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner after signing consent, during the study, and at least 30 days after the EoS visit;
•Must agree to not donate ova for at least 30 days after EoS visi
1.Previous diagnosis/history to migraine(s ) in the last 5 years as assessed by the Investigator. Where there is a history of headache, it is up to the investigator’s discretion if the description of the headaches fits with a diagnosis of migraine;
2.History or presence of significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or major surgery within the past 3 months determined by the Investigator to be clinically significant (participants with resolved childhood asthma may be included in the study). Conditions reported in the past 3 months considered by the Investigator to be clinically significant but not exclusionary should be discussed and be in agreement with the Sponsor;
3.Current or history of psychiatric disease in the last 5 years. Cases of untreated depression may be included in the study in agreement with the Sponsor;
4.Current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications;
5.Suffer from frequent or recurrent infections (defined as greater than or equal to 3 occurrences in the 12 months preceding first study drug administration or 2 occurrences in the 6 months preceding first study drug administration);
6.Any history of malignant disease in the last 10 years (excludes surgically resected skin squamous cell or basal cell carcinoma);
7.Prior diagnosis or family history of Addison’s disease, any other adrenal, pituitary or autoimmune disease;
8.Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia;
9.Use of or plans to use systemic immunosuppressive (e.g., corticosteroids, methotrexate, azathioprine, cyclosporine) or immunomodulating medications (e.g., interferon) during the study or within 3 months prior to the first study drug administration (prior use of nasal sprays for hayfever may be permitted if used > 30 days prior to study drug administration or alternatively at the discretion of the Investigator);
10.History of risk factors for torsade de pointes (including a family history [in first-degree relatives] of long QT syndrome or sudden cardiac death) or a known arrythmia;
11.Liver function test results elevated more than 1.5-fold above the upper limit of normal (ULN) for gamma glutamyl transferase (GGT), bilirubin (total, conjugated and unconjugated), alkaline phosphatase (ALP), aspartate aminotransferase (AST) or alanine aminotransferase (ALT). Volunteers with ALP and/or ALT/AST above the limits specified may be included, at the discretion of the Investigator, if the levels are unaccompanied by clinical signs and are determined to be normal variants;
12.Positive test results for active human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies at the screening visit;
13.Presence or having sequelae of gastrointestinal, liver, kidney, or other conditions known to interfere with the absorption, distribution, metabolism, or excretion of drugs (prior gall bladder and/or appendix removal is not exclusionary if the procedure was undertaken greater than or equal to 3 months prior to study drug administration; if less than 3 months, history of such procedures may still be considered not exclusionary if it is deemed appropriate by the Investigator). Cholecystectomy and Gilbert’s Sy
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method