Single Ascending Dose and Multiple Ascending Dose Phase I study of PXS-4728A Administered Orally in Healthy Adult Males.

Phase 1

Completed

• Conditions: Chronic Obstructive Pulmonary Disease; Cystic Fibrosis; Respiratory - Chronic obstructive pulmonary disease; Respiratory - Other respiratory disorders / diseases

• Registration Number: ACTRN12614001326684
• Lead Sponsor: Pharmaxis Ltd.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-12-17
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Completed
• Sex: Male
• Target Recruitment: 72

Inclusion Criteria

healthy males.
- BMI - 18.5 to 30 kg/m2.
- no clinically relevant abnormality in an ECG; QTcF (QTc Fredericia’s correction) less than or equal to 450 ms, PR interval of 120-210 ms and a QRS duration less than or equal to 120 ms.
- adequate venous access.
- agree to use two approved methods of contraception from screening and until 30 days after administration of the study drug.
- has given written informed consent.

Exclusion Criteria

- clinically significant abnormal findings on the physical examination or medical history.
- clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, skin or cardiovascular disease.
- history of significant drug allergies/ allergic reaction or currently suffers from clinically significant systemic allergic disease.
- abnormal wound healing as the result of surgery or trauma.
- received or is anticipated to receive any prescription systemic or topical medication within 14 days prior to the start of dosing or within 5 half lives of the drug, whichever is greater, or use any complimentary or alternative medicine 48 hours prior to the start of dosing or within 5 half
lives of the drug whichever is greater (excluding paracetamol).
- systolic blood pressure <100 or >140 mmHg, diastolic blood pressure <50 or >90 mmHg and heart rate (HR) <55 or >95 bpm.
- ALT, AST or bilirubin >2x ULN.
- significant renal insufficiency, with an estimated
creatinine clearance less than 60 mL/min at screening.
- positive screening test for HbsAg or Hep C.
- history of drug abuse in the last 2 years.
- drink more than three (3) units of alcohol daily
- used nicotine-containing products within 6 weeks before screening and unable to abstain until study completion.
- consumed caffeine and/or xanthine products for at least 48 hours prior to admission to the clinical facility, and whilst confined to the clinical facility.
- consumption of grapefruit, grapefruit juice, star fruit, oranges, orange juice, Seville oranges, red wine or other alcohol within 7 days prior to administration of study drug.
- positive urine screen for drugs of abuse and alcohol breath test at screening and study check-in.
- receipt of blood or blood products, or loss or donation of 450 mL or more of blood within 90 days before the first dose administration.
- clinically significant abnormality detected on telemetry pre-dose.
- systemic infection other than coryza in the last week prior to dosing

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
1. To evaluate the safety and tolerability of single ascending or repeated oral doses of PXS-4728A:<br>a) Recording of adverse events throughout the study.<br>b) Change from baseline in:<br>- Electrocardiogram (ECG) readings<br>- Clinical monitoring of blood pressure (BP)<br>- Heart rate (HR)<br>- Laboratory assessments[Part A (SAD): Measurements to be taken daily up to Day 5 following dosing on Day 1.<br><br>Part B (MAD): Measurements to be taken daily up to Day 21 following dosing on Day 1. Dosing will be once daily from Day until Day 14.]

Secondary Outcome Measures

Name	Time	Method
1. To evaluate plasma pharmacokinetic parameters after single and repeat oral dosing of PXS-4728A:<br>a) AUC (0-t) and AUC (0-inf)<br>b) Cmax – maximum concentration<br>c) Tmax – time to maximum observed plasma drug concentration<br>d) t1/2 – Terminal half-life<br>e) Accumulation ratio (For Part B only)[Blood and urine assessments were carried out for PK analysis. <br><br>Part A: To be assessed 11 times on Day 1 and once on Day 2, 3, 4 and 5.<br><br>Part B: To be assessed 11 times on Day 1 and Day 14 and once on Day 2 and Day 15.];2. Assessment of plasma pharmacodynamic parameters after single and repeat dosing of PXS-4728A:<br>a) SSAO activity in plasma using enzymatic assay<br>b) SSAO concentration in plasma using ELISA method[Blood assessments were carried out for PD parameters.<br><br>Part A (SAD): To be assessed 11 times on Day 1 and once on Day 2, 3, 4 and 5.<br><br>Part B (MAD): To be assessed 11 times on Day 1, once on Day 2 and Day 3 and 7 times on Day 14.]