This is a first-in-human, single-blind, placebo-controlled, single-centre study designed to assess the safety and tolerability of PDNO in healthy male and female subjects. In addition, the exposure of 1,2 propanediol (PD) will be evaluated. There are 2 parts to the study: Part I: single ascending dose (SAD), 7 cohorts, 30 minutes intravenous (i.v.) infusion of placebo followed by 1-hour i.v. infusion of PDNO to assess safety, tolerability and PD exposure in healthy male and female subjects. Part II: ascending doses of PDNO in 2 cohorts, 30 minutes i.v. infusion of placebo followed by 3 ascending doses of PDNO in cohort 1 and 3 ascending doses of PDNO in cohort 2. The first 2 doses in each cohort will be i.v. infused for 30 minutes whereas the last will be i.v. infused for 3 hours to assess safety, tolerability and PD exposure in healthy male and female subjects. If indicated by emerging data and recommended by the internal safety review committee (iSRC), 2 additional dose groups/cohorts (4+4 subjects) may be added to Part I and 1 dose group/cohort (4 subjects) may be added to Part II.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
38
PDNO consists of propylene glycol (1,2-propanediol, PD) chemically combined with NO (to be donated). The drug substance is formulated as an inherent mixture of 4 structure analogues. The mixture consists of an equilibrium of the 2 regioisomers 1-(nitrosooxy) propan-2-ol and 2-(nitrosooxy) propan-1-ol. In addition, each regioisomer is a racemic mixture.
Placebo (NaCl, commercially available dilution solution for parenteral use, 9 mg/mL)
CTC Clinical Trial Consultants AB
Uppsala, Sweden
Safety and tolerability of PDNO following i.v. infusion to healthy volunteers, as measured by incidence of treatment-emergent AEs, SAEs, AESI, changes in vital signs, ECG abnormalities, and laboratory abnormalities.
* Treatment-emergent adverse events (AEs) * Treatment-emergent serious AEs (SAEs) * Treatment-emergent AEs of special interest (AESI) * Treatment-emergent changes in vital signs (blood pressure, pulse, oxygen saturation, respiratory frequency, body temperature) * Treatment-emergent electrocardiogram (ECG) abnormalities * Treatment-emergent laboratory abnormalities
Time frame: Through study completion (i.e., Day 8)
Exposure parameters for 1,2-propanediol (PD): area under the curve from time 0 to time t (AUC0-t)
Time frame: During 24 hours from start of dosing
Exposure parameters for 1,2-propanediol (PD): area under the curve from time 0 to infinity (AUC0-inf)
Time frame: During 24 hours from start of dosing
Exposure parameters for 1,2-propanediol (PD): maximum plasma concentration (Cmax)
Time frame: During 24 hours from start of dosing
Exposure parameters for 1,2-propanediol (PD): terminal elimination half-life (T1/2)
Time frame: During 24 hours from start of dosing
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