None listed
Conditions
Brief summary
This study is to look at how safe and well tolerated PRX-101 is and to assess how much PRX-101 gets into the blood. PRX-101 is being developed as a possible treatment for paroxysmal supraventricular tachycardia which is a heart condition where the heart suddenly starts beating much faster than normal for a short period of time. The main hypothesis of this study is that PRX-101 is safe and well tolerated in a healthy adult population and that the pharmacokinetic profile (the amount that gets into the blood and how long it takes to be cleared from the body) is the same as that of an intravenous formulation of verapamil hydrochloride. A secondary hypothesis is that PRX-101 will have effects on blood pressure and heart rate.
Interventions
Part 2 has two stages. It is estimated that 18 to 48 participants will be enrolled in Part 2. The final number of participants and the dose of PRX-101 will be determined based on the data from Part 1. In Stage 1 participants will be randomized to one of three sequences with the selected dose of PRX-101 (Dose A) given under fed and fasted conditions and after administration of a 10mg IV dose of verapamil HCl (V). The three drug sequences for Part 2 are Dose A Fed – V – Dose A Fasted, Dose A Fas
Part 2 has two stages. It is estimated that 18 to 48 participants will be enrolled in Part 2. The final number of participants and the dose of PRX-101 will be determined based on the data from Part 1. In Stage 1 participants will be randomized to one of three sequences with the selected dose of PRX-101 (Dose A) given under fed and fasted conditions and after administration of a 10mg IV dose of verapamil HCl (V). The three drug sequences for Part 2 are Dose A Fed – V – Dose A Fasted, Dose A Fasted - Dose A Fed – V, and V – Dose A Fasted – Dose A Fed. All participants will receive a single dose of study drug on Day 1, Day 3 and Day 5 according to their assigned sequence. All participants from Stage 1 will then proceed into Stage 2 where on Day 7 the participants will receive two doses of PRX-101 (Dose A) given under fasted conditions and separated by 30 minutes. On Day 8 participants will receive a single dose of PRX-101 (Dose A) administered under fasted conditions and 5 minutes prior to completing a cold pressor test. The cold pressor test is a test where the participant will be asked to hold their hand in an ice bath of cold water for up to 2 minutes.. All study drug will be given in the clinical research unit and adherence to the intervention will be through direct observation.
Sponsors
Phocus Pharmaceuticals, Inc.
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. Aged between 18 to 55 years of age (inclusive) at the time of signing the informed consent. 2. Deemed healthy as determined by medical history, physical examination, vital sign measurements, ECG, and laboratory safety tests performed at the Screening Visit and/or before the first dose of study drug. 3. Not lactating or pregnant as confirmed by a serum pregnancy test at Screening and negative urine pregnancy test before dosing (applies only to participants of child-bearing potential. 4. Has a blood pressure increase of 10-20mmHg on the cold pressor test (Part 2 only). 5. Body weight at least 50Kg (male) and 45Kg (female) and body mass index within the range 18-32 kg/m2 (inclusive) at Screening 6. Agrees to comply with contraceptive guidance 7. Capable of giving signed informed consent. 8. Negative severe acute respiratory syndrome SARS-CoV-2 (COVID-19) test prior to admission, if required per clinical research unit standards. 9. Smoke no more than 2 cigarettes, pipes, cigars, e-cigarettes, or equivalent per week, including nicotine products, from 3 months before Screening and is willing to abstain from smoking/using nicotine products during the confinement period. 10. Willing to refrain from over-the-counter or prescription medications or herbal, nutritional or dietary supplements from 14 days before first dose until the end of study assessments have been completed, except for oral contraceptives, hormone replacement therapy and limited use of paracetamol or in the case of necessary treatment of AEs. 11. Willing to refrain from alcohol and caffeine from 48 hours before the first dose through the last dose of study drug. 12. Agrees to be available for all study visits and cooperates fully with the requirements of the study protocol, including the schedule of assessments.
Exclusion criteria
1. Past or current history of moderate or severe psychiatric illness based on the physician’s judgement and as defined by the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). 2. Past or current history of mild, moderate, or severe substance abuse according to DSM-5 definition within the previous 5 years before Screening. 3. Past or current history of alcohol use disorder defined as an average daily intake >3 units, or an average weekly intake >21 units, where 1 unit is equivalent to 1 can or bottle (355mL) of beer, or 1 measure (25mL) of spirits, or 1 glass (175 mL) of wine within 5 years prior to screening. 4. History of acute illness, infectious condition (e.g., COVID-19 or influenza) or chronic disease within 14 days before Screening or at Day -1, or current signs and symptoms of any diseases or conditions that would make participation not be in the best interest (eg, compromise the well-being) of the participant. 5. Any history of cardiovascular, cerebrovascular, or peripheral vascular disease. 6. Active malignancy, or history of malignancy, excluding basal or squamous cell carcinoma of the skin, within 2 years before Screening. 7. Any known allergy or hypersensitivity to verapamil or to any of the excipients in the formulation. 8. Use or intend to use any prescription medications/products within 14 days prior to check-in on Day -1, unless deemed acceptable by the Investigator (or designee). 9. Use or intend to use slow-release medications/products considered to still be active within 14 days before check-in on Day -1, unless deemed acceptable by the Investigator (or designee). 10. Use or intend to use any nonprescription medications/products including vitamins, minerals, and phytotherapeutic-/herbal-/plant-derived preparations within 7 days before check-in on Day 1, unless deemed acceptable by the Investigator (or designee) 11. Received treatment with another investigational drug, investigational device, or approved therapy for investigational use within 30 days or 5 half-lives (whichever is longer) before Screening 12. Immunized with a live-attenuated vaccine within 30 days before Screening. 13. Prior exposure to PRX-101 14. Positive alcohol breath test or urine test for drugs of abuse at screening and at the time of admission 15. Positive serology panel. 16. Clinically significant vital sign measurements at Screening. 17. Clinically significant laboratory abnormalities 18. Clinically significant history or presence of ECG findings 19. Poor venous access. 20. Donated blood or plasma within 30 days before Screening, lost more than 500 mL of whole blood within the 30 days before Screening, or received a blood transfusion within 1 year before Screening. 21. From a vulnerable population as defined by International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guideline for Good Clinical Practice (GCP) E6 (R2)
Outcome results
None listed