A Randomized, Double-blind, Double-dummy, Placebo-controlled, Therapeutic Exploratory Clinical Trial to Evaluate the Efficacy and Safety of DA-8031 After Oral Administration in Male Patients With Premature Ejaculation
This study is designed to evaluate the efficacy and safety of DA-8031 and to decide the optimal dose of DA-8031 in male patients with premature ejaculation after oral administration on-demand. The investigators hypothesized that newly-developed DA-8031 would effect in delaying ejaculation in patients with premature ejaculation (PE). Design: Placebo-controlled, Randomized, Double-blind, Double-dummy, Parallel group, Fixed dose design
A Dose Block-randomized, Double-blind, Placebo-controlled, Single/Multiple Dosing, Dose-escalation Clinical Trial to Investigate the Safety, Tolerability, and Pharmacokinetic Characteristics of DA-8031 After Oral Administration in Healthy Male Subjects
This is a dose block-randomized, double-blind, placebo-controlled, single/multiple dosing, dose-escalation study. The study is designed to describe the relationship between multiple doses and pharmacokinetic parameters of DA-8031 as well as safety profile.
2021-01-01·Drug design, development and therapy3区 · 医学
Pharmacokinetics, Tolerability and Pharmacogenetics of DA-8031 After Multiple Ascending Doses in Healthy Male Subjects.
3区 · 医学
作者: Sejung Hwang ; Dae Young Lee ; Joo-Youn Cho ; Jae-Yong Chung ; In-Jin Jang ; Kyung-Sang Yu ; SeungHwan Lee
DA-8031 is a novel selective serotonin reuptake inhibitor for the treatment of premature ejaculation. This study investigated the pharmacokinetics, safety and tolerability of multiple oral doses of DA-8031. In addition, a genetic analysis was explored to evaluate the effect of genetic polymorphisms on the pharmacokinetics of DA-8031.
Subjects and Methods:
A dose block-randomized, double-blind, placebo-controlled study was conducted in 3 dose groups with 20, 30 and 40 mg of DA-8031. Healthy male subjects were randomized to DA-8031 or placebo at a 4:1 ratio in each dose group of 10 subjects by oral administration once daily for 7 consecutive days. Serial blood and urine samples were collected for the pharmacokinetic evaluation, and the pharmacokinetic-related genes were analyzed by DMETTM plus. A safety evaluation was conducted including adverse events (AEs) monitoring and 12-lead electrocardiogram (ECG).
The plasma DA-8031 concentration reached the maximum concentration (Cmax) in 2.2 to 3.0 h and was eliminated with a mean half-life of 25.5 to 26.7 h at steady state. The accumulation index of DA-8031 ranged 2.3 to 2.8. The systemic exposure of DA-8031 of the CYP2D6 intermediate metabolizer (IM) was significantly higher compared to the CYP2D6 poor metabolizer (PM). There were no clinically significant QTc interval changes, and all the adverse events were mild.
After multiple oral doses of DA-8031 20, 30, and 40 mg in this study, the systemic exposure of DA-8031 increased in a more than dose-proportional manner with the increasing doses, and DA-8031 was generally well tolerated. In addition, the genetic polymorphisms of CYP2D6 have an impact on the pharmacokinetics of DA-8031.
2017-01-01·Drug design, development and therapy3区 · 医学
Pharmacokinetics and tolerability of DA-8031, a novel selective serotonin reuptake inhibitor for premature ejaculation in healthy male subjects.
3区 · 医学
作者: Dongseong Shin ; SeungHwan Lee ; Sojeong Yi ; Seo Hyun Yoon ; Joo-Youn Cho ; Mi Young Bahng ; In-Jin Jang ; Kyung-Sang Yu
DA-8031 is a selective serotonin reuptake inhibitor under development for the treatment of premature ejaculation. This is the first-in-human study aimed at evaluating the pharmacokinetics and tolerability of DA-8031 and its metabolites (M1, M2, M4, and M5) in the plasma and urine after administration of a single oral dose in healthy male subjects.
A dose block-randomized, double-blind, placebo-controlled, single ascending dose study was conducted. Subjects received either placebo or a single dose of DA-8031 at 5, 10, 20, 40, 60, 80, or 120 mg. DA-8031 and its four metabolites were analyzed in the plasma and urine for pharmacokinetic evaluation. The effect of genetic polymorphisms of cytochrome-P450 (CYP) enzymes on the pharmacokinetics of DA-8031 was evaluated.
After a single dose, plasma DA-8031 reached the maximum concentration at a median of 2-3 h and was eliminated with terminal elimination half-life of 17.9-28.7 h. The mean renal clearance was 3.7-5.6 L/h. Dose-proportional pharmacokinetics was observed over the dose range of 20-80 mg. Among the metabolites, M4 had the greatest plasma concentration, followed by M5 and M1. Subjects with CYP2D6 intermediate metabolizer had significantly greater dose-normalized Cmax and AUC0-t of DA-8031 as well as smaller metabolic ratios than those subjects with CYP2D6 extensive metabolizer. The most common adverse events were nausea, dizziness, and headache, and no serious adverse events were reported.
In conclusion, the systemic exposure of DA-8031 was increased proportionally to the dose within 20-80 mg. Genetic polymorphisms of CYP2D6 had an effect on the systemic exposure of DA-8031. DA-8031 was well tolerated after single doses of 80 mg or less.
2016-02-01·Urology3区 · 医学
New Therapeutic Perspectives in Premature Ejaculation.
3区 · 医学
作者: Joana Simões Paço ; Bruno Jorge Pereira
To review potential therapeutic targets and future therapeutic molecules in premature ejaculation (PE). PE is the most prevalent sexual dysfunction and affects about 23% of the male population. It is a universal disorder: it is independent of age and social or marital status. Men with PE typically refer associated comorbidities and report a significant impact not only on their quality of life but also on the satisfaction of the partner. Although common and treatable in most cases, the drugs currently available may affect sexual spontaneity and the cost can prove to be a hindrance.
MATERIALS AND METHODS:
A comprehensive literature revision was performed using PubMed and Scopus to identify relevant articles published in the fields of PE and its treatment until May 2015.
The main central targets identified include serotonergic, dopaminergic, and oxytocinergic neurotransmitters, opioid receptors, and mechanisms involved in the control of the spinal ejaculatory generator, located at the T12-L1-2 spinal cord level. On the other hand, peripheral interventions at semen's transport may also delay ejaculation by decreasing sequential contractions of the epididymis, vas deferens, seminal vesicles, prostate, and bladder neck.
There is a wide range of future options with regard to the treatment of PE. Molecules like DA-8031, Promescent, silodosin, Botulinum toxin-A, and resiniferatoxin may be near future treatments for this disorder.