NRD135S.E1, a nonopioid drug, was found to be well tolerated among patients with painful diabetic peripheral neuropathy, according to study findings published in Clinical Pharmacology in Drug Development.
For the current study, researchers reviewed data from 3 phase 1 studies conducted in Israel and Germany. Study participants received NRD135S.E1 in a single-ascending dose study (n=32), multiple-dose study (n=9), and food interaction study (n=16). The primary objectives of these studies were to evaluate safety, tolerability, and pharmacokinetics of NRD135S.E1.
Participants across the 3 studies had a mean age of 24.1 to 52.9 years, and the single- and multiple-dose studies included only men.
After single doses of NRD135S.E1 at 300 to 1200 mg, the mean time to maximum concentration and elimination half-life were 0.38 to 0.54 and 0.52 to 0.62 hours, respectively. Some subjects had a secondary peak 6 or more hours after dosing with a 0.4% to 0.9% of primary peak concentration.
A small fraction (0.15%-0.36%) of oral NRD135S.E1 was unchanged and eliminated in urine collected 0 to 6 hours after ingestion.
With multiple dosing, the maximum concentration and area under the curve (AUC) from time 0 to last quantifiable concentration (AUC0-t) was 23.9% and 31.0% higher on day 5 compared with day 1, respectively.
In the food interaction study, absorption was slower (median, 1.50 vs 0.75 h), exposure was higher (geometric mean AUC, 54.6 vs 39.4 mg •h/L), and the secondary peak was smaller (0.7% vs 5.5% of primary peak) during the fed condition.
These effects were dependent on sex, in which women had little changes in maximum concentration in fed and fast conditions (mean, 17.9 vs 17.6 mg/L), while men had decreased concentrations in the fed condition (mean, 14.9 vs 25.7 mg/L), respectively.
No participants discontinued treatment prematurely.
In the single-dose study, treatment-emergent adverse events (TEAE) were reported by 25% of NRD135S.E1 and 25% of placebo recipients. All events were mild and resolved. In the multiple-dose study, TEAE were reported by 22.2% of NRD135S.E1 and 0% of placebo recipients. All events were mild. One event of headache was deemed to be related to the study drug. In the food interaction study, TEAE were drug-related for 10 individuals in the fasted condition and 4 individuals in the fed condition. The most common events were headache (n=7), blood pressure increase (n=5), and sinus bradycardia (n=4).
The major limitation of these studies was the small sample sizes.
“Overall, the phase 1 studies … show rapid absorption and availability of [NRD135S.E1] without signs of relevant accumulation over multiple administrations as capsules or signs of dose-limiting toxicities; hence, further evaluation of [NRD135S.E1] in phase 2 studies in patients with [painful diabetic peripheral neuropathy] is warranted,” the study authors noted.
Disclosure: This research was supported by Novaremed Ltd. Some study authors declared affiliations with Novaremed. Please refer to the original article for a full list of disclosures.
Tiecke E, Rainisio M, Guentert T, et al. First-in-Human Single-Ascending-Dose, Multiple-Dose, and Food Interaction Studies of NRD.E1, an Innovative Nonopioid Therapy for Painful Diabetic Peripheral Neuropathy. Clin Pharmacol Drug Dev. Published online June 14, 2022. doi:10.1002/cpdd.1103