A randomised, double-blind, placebo-controlled, phase 1 study to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple ascending doses of PMX205 in healthy volunteers.
- Conditions
- Neurological - Parkinson's diseaseNeurological - Alzheimer's diseaseMotor Neuron DiseaseParkinson's DiseaseInflammatory and Immune System - Other inflammatory or immune system disordersNeurological - Neurodegenerative diseases
- Registration Number
- ACTRN12619001639112
- Lead Sponsor
- Alsonex Pty Ltd
- Brief Summary
The study results demonstrated PMX205 is safe to be administered to healthy volunteers and that at the doses selected PMX205 engaged with the biochemical target.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Male
- Target Recruitment
- 46
1.Male volunteers 18-55 years of age.
2.Able and willing to provide written informed consent prior to the performance of any study-specific procedures.
3.BMI between 18 and 32 kg/m2, inclusive.
4.Healthy as determined by medical history, physical examination, vital signs and 12-lead ECG at screening and day -1.
5.All clinical laboratory tests of blood and urine must be within the normal range or show no clinically relevant deviations as judged by the Investigator.
6.Non-smokers, ex-smokers (who have ceased smoking > 6 months prior to the screening visit and have no more than one pack-year history of smoking), or social smokers (no more than 5 cigarettes or equivalent per week and willing to refrain from smoking and using tobacco or nicotine products during the confinement periods).
1.Any history or presence of clinically relevant respiratory, gastrointestinal, renal, hepatic, haematological, lymphatic, neurological, cardiovascular, metabolic, psychiatric, musculoskeletal, genitourinary, immunological, dermatological, endocrine or other disease that, in the opinion of the Investigator, would impact on the study or the safety of the subjects..
2.Plasma creatinine, Plasma bilirubin, and ALT or AST > upper limit of normal (ULN), which is determined by the Investigator to be clinically significant. An exception is subjects with Gilbert’s syndrome, who are excluded if plasma bilirubin is > 1.5 × ULN.
3.Positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody or human immunodeficiency virus (HIV)-1 or HIV-2 antibody at screening.
4.Normal ECG findings or normal variants as determined by the Investigator, with QTc range less than or equal to 450 ms (Fridericia’s correction) at Screening and Day 1.
5.A family history of congenital long QT syndrome or unexplained sudden cardiac death.
6.History of malignancy, except for curatively treated basal cell carcinoma, squamous cell skin cancer or in-situ cervical carcinoma.
7.Use of prescription medications within 14 days prior to study drug administration.
8.Use of over-the-counter medication, vitamins or other food supplements, or herbal medications within 7 days prior to study drug administration. Exceptions are analgesics for minor ailments (e.g., paracetamol and/or ibuprofen up to 2 gm/day and 1.2 gm/day, respectively) and vitamins at standard replacement doses.
9.Intake of grapefruit (including its juice) from 48 hours prior to admission to the clinical research unit.
10.Previous treatment with PMX205 or other complement system inhibitor, including drugs such as Eculizumab.
11.Presence of an elevated body temperature or other possible sign of an active/acute infection at screening or admission to the clinical trial unit, which is determined by the Investigator to be clinically significant.
12.Clinically significant history of chronic or recurrent infections, including opportunistic infections.
13.History of splenectomy.
14.Use of systemic immunosuppressive medications in the past 2 years.
15.Received an investigational therapy within 30 days (or 5 half-lives, whichever is longer) prior to PMX205 administration.
16.History of clinically-significantclinically significant allergic reactions or anaphylaxis, including or any hypersensitivity to penicillins, cephalosporins and related antibiotics.
17.History of alcohol or drug abuse.
18.Positive screen for drugs of abuse (including amphetamines, methamphetamines, methadone, barbiturates, benzodiazepines, cocaine, opiates, methylenedioxymethamphetamine, phencyclidine, tetrahydrocannabinolopiates, cocaine, amphetamines, MDMA, cannabinoids, barbiturates and benzodiazepines) or alcohol at screening and day -1. At the Investigator’s discretion, the drug screen test may be repeated in the possible instance of a false positive due to e.g., poppy seed consumption.
19.Average intake of more than 14 units of alcohol per week (1 unit of alcohol equals approximately 250 mL of beer, 100 mL of wine or 35 mL of spirits).
20.Donation or loss of more than 400 mL of blood within 60 days prior to study drug administration.
21.Undergone major surgery in the 6 months prior to screening.
22.Any condition which could confound the results of the study, interfere with participation in the
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Safety outcome measures: Adverse events (evaluated according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0), vital signs, physical examinations, 12-lead ECGs and clinical laboratory tests.[Baseline, 24 hours (primary timepoint) and thereafter on Days 2 and 3 with additional follow up on Day 8, and further follow up on Days 15 and 29 from the commencement of treatment.<br>Vital signs on day 1 performed within 30 mins (± 3 mins) prior to dosing; then at 30 and 60 (± 3 mins); and 2, 4, and 8 hours (± 10 mins) after dosing.]
- Secondary Outcome Measures
Name Time Method