madman
Super Moderator
* KH-001 is an alkaloid derived from the South African Kanna plant and functions as a selective, high-potency serotonin reuptake transporter (SERT) inhibitor and phosphodiesterase inhibitor.
* The starting dose of 0.5 mg was selected based on anticipated sub-therapeutic levels. Dose escalation proceeded up to 62.5 mg, with intermediate doses of 2.5 mg and 12.5 mg for oral administration. Oral ingestion resulted in KH-001 concentrations generally below the limit of quantification, except at the highest dose (62.5 mg), indicating extensive first-pass metabolism. In contrast, its metabolite KH-160 was detected at all dose levels and increased with dose, confirming rapid intestinal and/or hepatic metabolism. Holding in the mouth oral administration resulted in significantly higher systemic KH-001 exposure, with a time to maximum concentration (Tmax) of 15–20 minutes and no measurable levels after 4 hours, supporting a rapid onset and clearance suitable for on-demand use. Importantly, no accumulation of KH-001 was observed with repeat dosing. Oral doses held in the mouth of 5–10 mg were well tolerated with no adverse events reported. At 12.5 mg and 15 mg, some subjects reported mild and transient AEs, including nausea and light-headedness. No serious adverse events occurred
* Pharmacokinetic data demonstrated effective systemic exposure via the holding in the mouth route, with reduced levels of the metabolite KH-160 and favourable onset and duration characteristics.
Dr Gruss , H1; Protzko, R2; Woodfinden, L2; Boghossian, J2; Koch, A3
1 - Kadence Bio
2 - Kanna Health Ltd trading as Kadence Bio
3 - Simbec-Orion - Clinical Pharmacology
Introduction
KH-001 besylate is a novel, botanically derived drug product developed for the on-demand treatment of premature ejaculation. KH-001 is an alkaloid derived from the South African Kanna plant and functions as a selective, high-potency serotonin reuptake transporter (SERT) inhibitor and phosphodiesterase inhibitor. In preclinical studies using the para-chloramphetamine-induced ejaculation model in male Wistar rats, KH-001 significantly and dose-dependently increased ejaculation latency and reduced the proportion of ejaculating animals.
Objective
To evaluate the first human exposure to KH-001 besylate oral solution in healthy male volunteers, focusing on pharmacokinetics (PK), safety, and tolerability.
Methods
A first-in-human Phase 1 clinical study was conducted in 74 healthy male volunteers to assess the single and multiple-dose PK profiles, safety, and tolerability of KH-001 besylate following oral administration. The study, approved by the local ethics committee and the UK regulatory authority (MHRA), was carried out at a specialized Phase 1 unit in the UK. In the single ascending dose (SAD) part of the study, cohorts of eight subjects (including two placebo recipients) received KH-001 besylate at doses ranging from 0.5 mg to 62.5 mg via oral administration. Pharmacokinetic sampling was performed over 24 hours post-dose. Safety assessments included monitoring for adverse events (AEs), vital signs, electrocardiograms (ECG) and routine blood and chemistry panels. Pharmacokinetic analysis was performed for KH-001 and its primary metabolite, KH-160, using a validated HPLC assay. Additional SAD cohorts were evaluated with holding in the mouth of the oral solution for 3 minutes from 5 mg to 15 mg. A multiple-dose evaluation was conducted in cohorts of nine subjects (including three placebo), who received repeat dosing of the oral solution over five days
Results
The starting dose of 0.5 mg was selected based on anticipated sub-therapeutic levels. Dose escalation proceeded up to 62.5 mg, with intermediate doses of 2.5 mg and 12.5 mg for oral administration. Oral ingestion resulted in KH-001 concentrations generally below the limit of quantification, except at the highest dose (62.5 mg), indicating extensive first-pass metabolism. In contrast, its metabolite KH-160 was detected at all dose levels and increased with dose, confirming rapid intestinal and/or hepatic metabolism. Holding in the mouth oral administration resulted in significantly higher systemic KH-001 exposure, with a time to maximum concentration (Tmax) of 15–20 minutes and no measurable levels after 4 hours, supporting a rapid onset and clearance suitable for on-demand use. Importantly, no accumulation of KH-001 was observed with repeat dosing. Oral doses held in the mouth of 5–10 mg were well tolerated with no adverse events reported. At 12.5 mg and 15 mg, some subjects reported mild and transient AEs, including nausea and light-headedness. No serious adverse events occurred. Vital signs, ECGs, and laboratory results showed no systemic changes attributable to KH-001.
Conclusions
KH-001 besylate, administered as a solution, was safe and well tolerated, with only mild, rapidly resolving and expected AEs consistent with known SERT inhibitor profiles. Pharmacokinetic data demonstrated effective systemic exposure via the holding in the mouth route, with reduced levels of the metabolite KH-160 and favourable onset and duration characteristics. These results support the PK, safety, and tolerability of KH-001 besylate and warrant further clinical investigation of its use as an on-demand treatment for premature ejaculation.
* The starting dose of 0.5 mg was selected based on anticipated sub-therapeutic levels. Dose escalation proceeded up to 62.5 mg, with intermediate doses of 2.5 mg and 12.5 mg for oral administration. Oral ingestion resulted in KH-001 concentrations generally below the limit of quantification, except at the highest dose (62.5 mg), indicating extensive first-pass metabolism. In contrast, its metabolite KH-160 was detected at all dose levels and increased with dose, confirming rapid intestinal and/or hepatic metabolism. Holding in the mouth oral administration resulted in significantly higher systemic KH-001 exposure, with a time to maximum concentration (Tmax) of 15–20 minutes and no measurable levels after 4 hours, supporting a rapid onset and clearance suitable for on-demand use. Importantly, no accumulation of KH-001 was observed with repeat dosing. Oral doses held in the mouth of 5–10 mg were well tolerated with no adverse events reported. At 12.5 mg and 15 mg, some subjects reported mild and transient AEs, including nausea and light-headedness. No serious adverse events occurred
* Pharmacokinetic data demonstrated effective systemic exposure via the holding in the mouth route, with reduced levels of the metabolite KH-160 and favourable onset and duration characteristics.
Dr Gruss , H1; Protzko, R2; Woodfinden, L2; Boghossian, J2; Koch, A3
1 - Kadence Bio
2 - Kanna Health Ltd trading as Kadence Bio
3 - Simbec-Orion - Clinical Pharmacology
Introduction
KH-001 besylate is a novel, botanically derived drug product developed for the on-demand treatment of premature ejaculation. KH-001 is an alkaloid derived from the South African Kanna plant and functions as a selective, high-potency serotonin reuptake transporter (SERT) inhibitor and phosphodiesterase inhibitor. In preclinical studies using the para-chloramphetamine-induced ejaculation model in male Wistar rats, KH-001 significantly and dose-dependently increased ejaculation latency and reduced the proportion of ejaculating animals.
Objective
To evaluate the first human exposure to KH-001 besylate oral solution in healthy male volunteers, focusing on pharmacokinetics (PK), safety, and tolerability.
Methods
A first-in-human Phase 1 clinical study was conducted in 74 healthy male volunteers to assess the single and multiple-dose PK profiles, safety, and tolerability of KH-001 besylate following oral administration. The study, approved by the local ethics committee and the UK regulatory authority (MHRA), was carried out at a specialized Phase 1 unit in the UK. In the single ascending dose (SAD) part of the study, cohorts of eight subjects (including two placebo recipients) received KH-001 besylate at doses ranging from 0.5 mg to 62.5 mg via oral administration. Pharmacokinetic sampling was performed over 24 hours post-dose. Safety assessments included monitoring for adverse events (AEs), vital signs, electrocardiograms (ECG) and routine blood and chemistry panels. Pharmacokinetic analysis was performed for KH-001 and its primary metabolite, KH-160, using a validated HPLC assay. Additional SAD cohorts were evaluated with holding in the mouth of the oral solution for 3 minutes from 5 mg to 15 mg. A multiple-dose evaluation was conducted in cohorts of nine subjects (including three placebo), who received repeat dosing of the oral solution over five days
Results
The starting dose of 0.5 mg was selected based on anticipated sub-therapeutic levels. Dose escalation proceeded up to 62.5 mg, with intermediate doses of 2.5 mg and 12.5 mg for oral administration. Oral ingestion resulted in KH-001 concentrations generally below the limit of quantification, except at the highest dose (62.5 mg), indicating extensive first-pass metabolism. In contrast, its metabolite KH-160 was detected at all dose levels and increased with dose, confirming rapid intestinal and/or hepatic metabolism. Holding in the mouth oral administration resulted in significantly higher systemic KH-001 exposure, with a time to maximum concentration (Tmax) of 15–20 minutes and no measurable levels after 4 hours, supporting a rapid onset and clearance suitable for on-demand use. Importantly, no accumulation of KH-001 was observed with repeat dosing. Oral doses held in the mouth of 5–10 mg were well tolerated with no adverse events reported. At 12.5 mg and 15 mg, some subjects reported mild and transient AEs, including nausea and light-headedness. No serious adverse events occurred. Vital signs, ECGs, and laboratory results showed no systemic changes attributable to KH-001.
Conclusions
KH-001 besylate, administered as a solution, was safe and well tolerated, with only mild, rapidly resolving and expected AEs consistent with known SERT inhibitor profiles. Pharmacokinetic data demonstrated effective systemic exposure via the holding in the mouth route, with reduced levels of the metabolite KH-160 and favourable onset and duration characteristics. These results support the PK, safety, and tolerability of KH-001 besylate and warrant further clinical investigation of its use as an on-demand treatment for premature ejaculation.
