Abstract Details

Title Pharmacokinetics and Safety of STS101, A Novel Investigational Dihydroergotamine Powder Drug-Device Combination in Healthy Subjects

Topic Headache

Presentation(s) P13 - Poster Session 13 (8:00 AM-9:00 AM)

Poster/Presentation
Number 15-003

Background STS101 (DHE nasal powder) is a novel, investigational drug-device combination product. A previous PK study demonstrated STS101 was well tolerated and achieved systemic drug exposure comparable to IM DHE mesylate 1.0 mg. This study compares the PK and safety profile of STS101, incorporating an optimized delivery device, with DHE LNS and IM DHE.

Objective To evaluate safety and pharmacokinetics of dihydroergotamine (DHE) of DHE nasal powder (STS101), DHE mesylate liquid nasal spray (DHE LNS), and intramuscular DHE mesylate injection (IM DHE) in healthy subjects.

Design/Methods This is a randomized, open-label, 5-period crossover study. Thirty-six healthy subjects were administered single doses of STS101 5.2 mg, DHE LNS 2.0 mg, and IM DHE 1.0 mg. Blood samples to determine concentrations of DHE were obtained pre-dose and up to 48 hours post-dose. Vital signs, physical examinations, nasal examinations, and adverse event assessments were performed.

Results

C_max was 2230, 3730, and 673 pg/mL for STS101, IM DHE, and DHE LNS, respectively. DHE plasma concentrations rose rapidly after STS101 and IM DHE, with mean concentration greater than 2000 pg/mL at 20 and 5 minutes, respectively. AUC_0-inf reached 10900, 13900, and 4240 h*pg/mL for STS101, IM DHE, and DHE LNS, respectively. The PK variability of STS101 was substantially lower than for DHE LNS.

TEAEs were reported by 14.3%, 29.4% and 11.8% for STS101, IM DHE, and DHE LNS, respectively. No serious adverse events occurred.

Conclusions STS101 demonstrated rapid and prolonged absorption facilitating high plasma concentrations within 20 minutes, AUC_0-2h values 3-fold greater than DHE LNS, and AUC_0-inf comparable to IM DHE. STS101 showed a favorable tolerability profile.

Authors/Disclosures
Detlef Albrecht PRESENTER	Detlef Albrecht has received personal compensation for serving as an employee of Satsuma. Detlef Albrecht has stock in Satsuma.
Richard B. Lipton, MD, FAAN (Albert Einstein College of Medicine)	Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Lundbeck. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for GlaxoSmithKline. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Teva. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vedanta. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Pfizer. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Axon. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Satsuma. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cool Tech. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BDSI. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Linpharma. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan/Abbvie. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Lipton has stock in Biohaven. Dr. Lipton has stock in Manistee. Dr. Lipton has stock in Axon. Dr. Lipton has stock in CoolTech. The institution of Dr. Lipton has received research support from Teva. The institution of Dr. Lipton has received research support from Amgen. The institution of Dr. Lipton has received research support from Allergan/Abbvie. The institution of Dr. Lipton has received research support from Gammacore. The institution of Dr. Lipton has received research support from Axsome. The institution of Dr. Lipton has received research support from Charleston Labs. The institution of Dr. Lipton has received research support from Eli Lilly. The institution of Dr. Lipton has received research support from Satsuma. The institution of Dr. Lipton has received research support from NIH . The institution of Dr. Lipton has received research support from Veterans Administration. Dr. Lipton has received publishing royalties from a publication relating to health care.
Shannon Strom	Shannon Strom has received personal compensation for serving as an employee of Satsuma Pharmaceuticals. Shannon Strom has received personal compensation in the range of $0-$499 for serving as a Consultant for Arena Pharmaceuticals. Shannon Strom has stock in Satsuma Pharmaceuticals.