CompletedPhase 1ACTRN12616000050459

Crossover Comparison of the Tolerability and Pharmacokinetics of ZP-Zolmitriptan Intracutaneous Microneedle System with Oral Zolmitriptan and Subcutaneous (SC) Sumatriptan in Healthy Volunteers

Crossover Comparison of the Tolerability and Pharmacokinetics of ZP-Zolmitriptan Intracutaneous Microneedle System with Oral Zolmitriptan and SC Sumatriptan in Healthy Volunteers

Sponsor

Pharmaceutical Solutions Ltd

Enrollment

20 participants

Start Date

Aug 19, 2015

Study Type

Interventional

Conditions

Migraine

Summary

Zolmitriptan is a 5HT1 agonist widely used for the treatment of migraine. Like other compounds in the triptan class, it has been shown to be effective and well-tolerated in placebo-controlled clinical trials. Zolmitriptan is available as a conventional release tablet (2.5 mg and 5.0 mg), a “fast melt” orally disintegrating tablet (2.5 mg and 5.0 mg) and a nasal spray (5.0 mg). The last two formulations were developed to potentially provide a more rapid onset of effect than the conventional release tablet, as speed of onset is an attribute that patients often cite as important in migraine relief products. The bioavailability of zolmitriptan conventional release tablets has been found to be between 41 and 48% mainly due to first-pass metabolism. Therefore, a product which which avoided first-pass metabolism, the potential for food interaction and lesser absorption during a migraine could have advantages over existing zolmitriptan formulations. Additionally, an important consideration for a non-oral formulation of zolmitriptan is the high incidence of nausea that occurs during a migraine attack. In 60-70% of migraine attacks, nausea is a significant symptom that patients experience. Hence, a product that can be administered without using the gastrointestinal system (and not being susceptible to being vomited up) could be advantageous for the subject experiencing a migraine. The aim of this study is to compare the pharmacokinetics of the parent compound and the metabolites, and tolerability of various doses of intracutaenous zolmitriptan doses to a standard oral dose (2.5 mg) of zolmitriptan. The study will provide preliminary information on the potential advantages of the ZP-Zolmitriptan system use for the treatment of migraine.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 60 Yearss

Inclusion Criteria4

Women or men 18 to 60 years of age
Absence of significant health issues
Systolic BP (measured after remaining supine for 5 minutes) inclusive of 90 and 160 mmHg and diastolic BP inclusive of 50 and 95 mmHg.
Body mass index (BMI) of less than or equal to 32 kg/m2

Exclusion Criteria19

Evidence or significant history of hepatic, reproductive, gastrointestinal, renal, bleeding, or hematological disorders including coagulation, pulmonary, neurological, respiratory, endocrine, or cardiovascular system abnormalities (especially hypertension, coronary artery disease or cardiac rhythm abnormalities), psychiatric disorders, acute infection, or other conditions that would interfere with study participation or with the absorption, distribution, metabolism, or excretion of drugs.
Presence of two or more risk factors for cardiovascular disease (family history of premature heart disease, hyperlipidemia, or hypertension)
History of contact dermatitis or known dermatological disorders that would interfere with the study procedures or assessments
Known allergy or sensitivity to tapes, adhesives, or zolmitriptan
Planned participation in activities which cause inflammation, irritation, sunburn, lesions, or tattoos at the intended application sites from 2 weeks prior to screening through their last day of study participation
Use of warfarin within 1 month prior to the first dose or heparin within 1 week prior to study drug administration
Use of prescription medications other than the following:
a. Hormone Replacement Therapy (HRT)
b. Proton Pump Inhibitors (PPIs)
c. Antihistamines
d. Intermittently used NSAIDs
e. Exceptions may be allowed on a case by case basis by the sponsor.
History of epilepsy or other seizure disorder
History of tobacco usage within the past year or greater than 10 pack-years lifetime (1 pack-year = 1 pack every day for a year)
Female patients must not be pregnant. Women in child-bearing age must use an effective means of contraception.
Body weight less than 55 kg
Use of any other investigational compound within one month of planned study drug dosing
On-going drug or alcohol abuse, or history of either deemed to be clinically significant by the investigator
Subjects who, in the opinion of the investigator, should not participate in the study, or may not be capable of following the study schedule for any reason

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Interventions

In this study, ZP-Zolmitriptan will be compared to oral zolmitriptan and SC sumatriptan. ZP-Zolmitriptan is a microneedle patch system consisting of a disposable microneedle patch and a reusable applicator. The user applies the patch by pressing the applicator/patch ring assembly onto the skin site on the upper arm. The ZP applicator is designed to ensure that the same force is applied across different users. Each of the 20 subjects will receive each of the treatments once (A-G) every 5 days i.e. 120 hours between dosing days. In Part 1, each of the subjects will be randomly assigned to one of the five treatments (A-E) on the first dosing day. On the second dosing day, they will be randomly assigned to one of the remaining four treatments. On dosing days 3,4, and 5, they will be randomly assigned to one of the other remaining treatments until all five treatments (A-E) have been taken by each of the subjects. On any dosing day, for the 20 subjects, four will receive Treatment A, four will receive Treatment B, four will receive Treatment C, four will receive Treatment D, and four will receive Treatment E. Treatment A: ZP-Zolmitriptan intracutaenous system MF 1663 0.48 mg Treatment B: Two patches of ZP-Zolmitriptan intracutaenous system MF 1663 0.48 mg Treatment C: ZP-Zolmitriptan intracutaenous system MF 1663 1.9 mg Treatment D: Zolmitriptan 2.5 mg tablet Treatment E: Sumitriptan Succinate 6.0 mg/0.5 mL for SC injection In Part 2, all subjects will receive Treatment F (ZP-Zolmitriptan intracutaenous system MF 1663 1.9 mg x2). Treatment F: Two patches of ZP-Zolmitriptan intracutaenous system MF 1663 1.9 mg In Part 3, all subjects will receive Treatment G (ZP-Zolmitriptan 3.8 mg). Treatment G: ZP-Zolmitriptan intracutaenous system MF 1790 3.8 mg For each treatment, drug is administered once. Treatments B and F consist of two patches that should be applied on the same arm as quickly as possible. All drug administration and application is done by the site staff. At the end of each dosing day, the safety data from the subjects will be evaluated. If tolerability is deemed to be acceptable by the Principal Investigator and sponsor representatives, a decision will be made to proceed to the next dosing day. All ZP-Zolmitriptan Patch System components are to be used only in accordance with this protocol under the supervision of the Investigator. The Investigator will maintain detailed and verifiable records that document the receipt, storage, dispensing, and return of all ZP-Zolmitriptan Patch System components provided by Zosano Pharma. These records will include a listing of which study drug supplies were dispensed for particular subjects treated in the study, by whom, when, and the specific quantities dispensed and remaining at the completion of the subject’s investigational treatment. Reasons for departure from the expected dispensing and dosing regimen will also be documented. All leftover used and unused study patches should be retained for drug accountability auditing to be performed by Zosano Pharma or its representatives. At the conclusion of the study, the study drug accountability records must accurately reflect the receipt and final disposition of all study drug shipped to the site. Destruction or return of remaining used and unused drug supplies by the study site will occur only upon receipt of written authorization by Zosano Pharma or its representatives.