Pharmacokinetics in Oral and Intranasal Formulations of Zolmitriptan.

Study Overview
=================
Brief Summary
-----------------
This is a phase I study to evaluate the PBPK of zolmitriptan intranasal versus oral administration.

Official Title
-----------------
Pharmacokinetic Model Based on Population Physiology of Oral and Intranasal Formulations of Zolmitriptan in Healthy Volunteers

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Drug: Zolmitriptan intranasal.
* Drug: Zolmitriptan oral.


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male or female volunteers by physical examination, vital signs, ECG, and safety laboratory parameters and results must be within normal ranges or considered not clinically relevant by the investigator. Age ≥ 18 years and ≤ 55 years. Body mass index (BMI) ≥ 18 and ≤ 30. Able/willing to accept restrictions regarding diet, physical exercise, and consumption of alcohol and/or xanthine-containing items when outside the Clinical Research Unit (CRU) Able to read Spanish and adhere to study requirements. Informed consent signed before any procedure required by the study. Exclusion Criteria: Smoking. History or clinically relevant diseases. Be under administrative or legal supervision. Pregnancy and breastfeeding. Positive blood or urine drug of abuse test or breathalyzer prior to study drug administration. Any history, disease, disorder, condition, anomaly or clinical finding that is relevant in the judgment of the investigator that may interfere with the study. Known hypersensitivity to any drug or excipient of the drug. Use of medications, inhibitors, any prescription or over-the-counter products, including herbs, homeopathy, vitamins, minerals, and nutritional supplements, before or during the study, that may interfere with the conduct and results of the study. Donation or transfusion of blood or plasma before, during or after study drug administration. History of inadequate venous access and/or experience of difficulty donating blood. Not being able/unwilling to accept restrictions regarding diet, physical exercise and consumption of alcohol and/or articles containing xanthine when outside the CRU. Subject included in a clinical study in the 3 months prior to the study drug administration.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Zolmitriptan intranasal.<br> | Drug: Zolmitriptan intranasal.<br>* Zolmitriptan nasal spray is supplied in a single-use, ready-to-use spray unit. It is administered in one nostril. The full protocol will explain how to use it. Following drug administration, study subjects will continue to fast for a minimum of 4h and snacks and standard meals may be served at scheduled times after drug administration (snack: +4h; lunch: +7h; snack: +10h). Liquid intake will not be allowed from 2h before to 2h after drug administration.<br>|
| Experimental: Zolmitriptan oral.<br> | Drug: Zolmitriptan oral.<br>* Zolmitriptan 5 mg orally disintegrating tablet is to be taken without liquids. For oral administration, each tablet will be placed in the top of the tongue without any liquid and will disperse in a matter of seconds, then be swallowed with saliva. Following drug administration, study subjects will continue to fast for a minimum of 4h and snacks and standard meals may be served at scheduled times after drug administration (snack: +4h; lunch: +7h; snack: +10h). Liquid intake will not be allowed from 2h before to 2h after drug administration.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of zolmitriptan on heart rate (HR). |  | Up to 24 hours. | 
| Effects of zolmitriptan on systolic and diastolic blood pressure (BP). |  | Up to 24 hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of zolmitriptan on vasoactive intestinal polypeptide (VIP) in captures Day 1. |  | Up to 24 hours. |