PRN473

An AE was defined as any untoward medical occurrence in a participant temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. SAEs were any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were AEs that occurred from the time of the first IMP in the safety analysis period.

Vital signs assessments included supine systolic blood pressure, supine diastolic blood pressure, supine heart rate (HR), and body temperature. Criteria for PCSA: Supine SBP: ≤ 95 mmHg and decrease from baseline ≥ 20 mmHg, ≥ 160 mmHg and increase from baseline ≥ 20 mmHg; Supine DBP : ≤ 45 mmHg and decrease from baseline ≥ 10 mmHg, ≥ 110 mmHg and increase from baseline ≥ 10 mmHg; Orthostatic SBP: ≤ -20 mmHg; Orthostatic DBP: ≤ -10 mmHg; Supine PR: ≤ 50 beats/min and decrease from baseline ≥ 20 beats/min, ≥ 120 beats/min and increase from baseline ≥ 20 beats/min; Weight :≥ 5% decrease from baseline, ≥ 5% increase from baseline

Criteria for PCSA: HR: less than (\<) 50 beats per minute (bpm), \> 90 bpm, \> 90 bpm and increase from baseline \> = 20 bpm, \> 100 bpm; PR interval: \> 200 milliseconds (msec), \> 200 msec and increase from baseline \>= 25 %, \> 220 msec; QRS interval: greater than (\>) 110 msec, \> 110 msec and increase from baseline greater than or equal to (\>=) 25%, \> 120 msec; QT interval: \> 500 msec; QTc interval \> 450 msec; \> 480 msec, increase from baseline (30-60) msec, increase from baseline \> 60 msec.

Criteria for PCSA: Hemoglobin (Hb) \<=115 grams per liter (g/L) (Male\[M\]) or \<=95 g/L (Female\[F\]), \>= 185 g/L (M) or \>=165 g/L (F), decrease from baseline \>= 20 g/L; Hematocrit: \<=0.37 volume/volume (v/v) (M) or \<=0.32 v/v (F), \>=0.55 v/v (M) or \>=0.5 v/v (F); Red blood cells (RBC): \>=6 Tera/L; Platelets: \< 100 Giga/L, \>=700 Giga/L; Neutrophils: \<1.5 Giga/L (Non-Black \[NB\]) or \<1.0 Giga/L (Black \[B\]); Lymphocytes: \> 4.0 Giga/L; Monocytes: \>0.7 Giga/L; Basophils: \>0.1 Giga/L; Eosinophils: \>0.5 Giga/L or \>upper limit of normal (ULN) (if ULN \>=0.5 Giga/L).

Criteria for PCSA: Sodium: \<=129 millimoles (mmol)/L, \>=160 mmol/L; Potassium: \<3 mmol/L, \>=5.5 mmol/L and Chloride: \<80 mmol/L, \>115 mmol/L.

Criteria for PCSA: Glucose: \<=3.9 mmol/L and \< lower limit of normal range (LLN); \>=11.1 mmol/L (unfasted \[unfas\]) or \>=7 mmol/L (fasted \[fas\]); Albumin: \<=25 g/L; Creatine kinase (CK): \> 3 ULN, \> 10 ULN; C-Reactive protein: \> 2 ULN or 10 mg(milligram)/L (if ULN not provided).

Criteria for PCSA: Creatinine: \>=150 micromoles per liter (mcmol/L), \>=30% change from baseline, \>=100% change from baseline.

Liver function parameters assessments included alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, lactate dehydrogenase, total bilirubin, direct bilirubin, and gamma glutamyl transferase (GGT).

Urinalysis parameters assessments included potential of Hydrogen (pH), urobilinogen, and specific gravity.

Grading of application-site local tolerability symptoms (burning, pruritus, and erythema) were recorded using the grading scale following each dosing during the double-blind period. Grading of application site tolerability symptoms graded from 0 (none) to 3 (severe).