A First-in-human Study to Assess the Safety and Tolerability of PDNO

Last updated on July 2021

Recruitment

Recruitment Status: Recruiting
Estimated Enrollment: Same as current

Summary

Conditions: Pulmonary Hypertension
Type: Interventional
Phase: Phase 1
Design: Allocation: Non-RandomizedIntervention Model: Sequential AssignmentIntervention Model Description: In Part I, each subject will receive a 30 minutes iv infusion of placebo followed by a 1 hour iv infusion of PDNO in parallel with a carrier sodium bicarbonate buffer, the infusion of which will start 5 minutes prior to start of placebo infusion and continue until 15 minutes after end of PDNO infusion. Between the end of placebo infusion and prior to the start of PDNO infusion, there will be a 20 minutes stabilisation period with infusion of sodium bicarbonate buffer only. In Part II, each subject will receive a 30 minutes iv infusion of placebo followed by 2 x 30 minutes infusion of PDNO at 2 ascending dose levels and one 3 hour infusion of PDNO at a third dose level.Masking: Single (Participant)Masking Description: During the administration the infusion set is masked for the subject.Primary Purpose: Treatment

Participation Requirements

Age: Between 18 years and 45 years
Gender: Both males and females

Description

Part I In Part I of the study, 4 subjects per cohort will first receive a 30 minutes iv infusion of placebo followed by a 1 hour iv infusion of PDNO in parallel with a continuous infusion of a sodium bicarbonate carrier buffer. A total of 7 sequential cohorts with the following tentative dose levels are planned: 0.3, 1.0, 3.0, 10, 30, 60 and 120 nmol/kg/min. Up to 2 additional dose levels can be explored, tentatively 180 and 240 nmol/kg/min. Lower, intermediate doses (e.g. 90 nmol/kg/min) or repeated doses may also be given, based on the safety and tolerability of the drug if recommended by the iSRC. The maximum dose in the study will not exceed 240 nmol/kg/min.Subjects will come for 4 visits to the clinic. Screening (Visit 1) will take place from Day -28 to Day -1 and will include the subjects' signing of the informed consent and an eligibility check. At Visit 2, subjects will be admitted to the clinic on Day -1 for pre-dose assessments. The subjects will be carefully monitored by clinical staff during and after infusion. Vital signs (including pulse oximetry) and ECG will be checked at regular intervals. During the infusion, blood pressure will be continuously controlled via intra-arterial blood pressure monitoring. In all cohorts, safety, tolerability and PD exposure will be assessed before, during and after the PDNO iv infusion. FeNO monitoring will be also be performed. Part II Part II of the study will explore ascending doses of PDNO in 2 cohorts. In each cohort, 4 subjects will first receive a 30 minutes iv infusion of placebo followed by iv infusions of PDNO in 3 ascending doses in parallel with a continuous infusion of a sodium bicarbonate carrier buffer. Each of the first 2 dose levels in each cohort will be iv infused for 30 minutes whereas the highest dose level will be iv infused for 3 hours. To avoid any potential rebound effect, there will be no stabilisation period between either dose escalation. The planned dose levels are: 1, 3 and 10 nmol/kg/min in cohort 1 and 30, 60 and 120 nmol/kg/min in cohort 2. The actual doses given in Part II will be based on emerging knowledge of safety and tolerability of PDNO observed in Part I of the study. The maximum dose in Part II will not exceed the highest dose given in Part I. One additional cohort with additional doses or dosing schemes to establish the target dose for subsequent studies can be explored based on the safety and tolerability of the drug if recommended by the iSRC.

Tracking Information

NCT #: NCT04891354
Collaborators: Not Provided
Investigators: Principal Investigator: Folke Sjöberg, MD CTC Clinical Trial Consultants AB