A Phase I Study to Study the PK and Safety of Single Doses of STS101, DHE Injection and Nasal Spray in Healthy Subjects

Study Overview
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Brief Summary
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Single-center, single-dose, open-label, 2-part, 3-period crossover (in each part), pharmacokinetic and safety study.

Detailed Description
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Phase 1, open-label, 2-part, single-dose pharmacokinetic and safety study of STS101 in healthy subjects. Part 1 was designed to identify a dose level of STS101 for administration in Part 2. Subjects in Part 1 received 3 ascending doses of STS101 in a 3-period crossover manner. During Part 2, subjects received the dose of STS101 selected from Part 1, 1.0 mg DHE mesylate IM injection, and 2 mg DHE mesylate nasal spray in a randomized, 3 period crossover manner.

Official Title
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A Randomized, Open-Label, Crossover Study to Evaluate the PK, Bioavailability, Dose Proportionality, Safety, and Tolerability of Single Doses of STS101, DHE Mesylate IM Injection and DHE Mesylate Nasal Spray in Healthy Adult Subjects

Conditions
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Migraine With Aura, Migraine Without Aura, Migraine

Intervention / Treatment
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* Drug: Dihydroergotamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 to 50 years of age at the time of enrollment. Signed the informed consent document. Subject judged to be healthy by a qualified physician Exclusion Criteria: Abnormal physical findings of clinical significance at the screening examination Significant abnormal laboratory values at the Screening Visit. Clinically significant symptoms or conditions that may have placed the subject at an unacceptable risk as a participant in the trial, or that may have interfered with the absorption, distribution, metabolism or excretion of the IMP.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STS101 1.5 mg<br>STS101 (dihydroergotamine nasal powder), 1.5 mg | Drug: Dihydroergotamine<br>* Dihydroergotamine is a semi-synthetic derivative of ergotamine tartrate.<br>* Other names: Dihydroergotamine Mesylate;|
| Experimental: STS101 3.0 mg<br>STS101 (dihydroergotamine nasal powder), 3.0 mg | Drug: Dihydroergotamine<br>* Dihydroergotamine is a semi-synthetic derivative of ergotamine tartrate.<br>* Other names: Dihydroergotamine Mesylate;|
| Experimental: STS101 6.0 mg<br>STS101 (dihydroergotamine nasal powder), 6.0 mg | Drug: Dihydroergotamine<br>* Dihydroergotamine is a semi-synthetic derivative of ergotamine tartrate.<br>* Other names: Dihydroergotamine Mesylate;|
| Active Comparator: DHE intramuscular injection<br>Dihydroergotamine mesylate | Drug: Dihydroergotamine<br>* Dihydroergotamine is a semi-synthetic derivative of ergotamine tartrate.<br>* Other names: Dihydroergotamine Mesylate;|
| Active Comparator: DHE nasal spray<br>Dihydroergotamine mesylate | Drug: Dihydroergotamine<br>* Dihydroergotamine is a semi-synthetic derivative of ergotamine tartrate.<br>* Other names: Dihydroergotamine Mesylate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| STS101 Dose Selection - Part 1 | To select a dose level of STS101 for further evaluation in Part 2 | Pre-dose through 48 hours post-dose | 
| DHE Relative Bioavailability - Part 2 | To assess the relative bioavailability of dihydroergotamine following a single dose of STS101 at the dose level selected in Part 1 compared to a single dose of 1 mg DHE administered by intramuscular injection and 2 mg DHE administered as nasal spray | Pre-dose through 48 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DHE Area Under the Curve [AUC] - Part 1 | To describe the pharmacokinetic profile based on the AUC of dihydroergotamine following single dose administration of 1.5 mg, 3.0 mg and 6.0 mg of STS101 | Pre-dose through 48 hours post-dose | 
| 8'OH-DHE Area Under the Curve [AUC] - Part 1 | To describe the pharmacokinetic profile based on the AUC of 8'hydroxydihydroergotamine (8'OH-DHE) following single dose administration of 1.5 mg, 3.0 mg and 6.0 mg of STS101 | Pre-dose through 48 hours post-dose | 
| Serious Adverse Events - Parts 1 & 2 | To assess the safety profile through examination of serious adverse events of single doses of STS101; 1 mg DHE administered by intramuscular injection, and 2 mg DHE administered as nasal spray | Pre-dose through 48 hours post-dose | 
| Treatment-Related Adverse Events - Parts 1 & 2 | To assess the safety profile through examination of treatment-related adverse events of single doses of STS101; 1 mg DHE administered by intramuscular injection, and 2 mg DHE administered as nasal spray | Pre-dose through 48 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dihydroergotamine, dihydroergotamine mesylate, migraine