Single-Dose Oral Apremilast 30 mg Induction of Headache and Migraine in Women with Migraine Without Aura: A Randomized, Placebo-Controlled Study

The primary objective is to evaluate the capacity of a single oral dose of apremilast 30 mg to provoke a migraine attack in female participants with a documented history of migraine without aura. This assessment addresses the safety profile of the phosphodiesterase‑4 inhibitor in a population predisposed to migraine, informing clinical risk evaluation.

The trial enrolled healthy women aged 18–65 years with a body weight of 50–90 kg who met diagnostic criteria for episodic migraine without aura according to the International Classification. Participants were required to use reliable contraception (hormonal methods, intrauterine devices, or oral contraceptives) throughout the study and to demonstrate fluency in Danish or English. Selection was based on documented history of the specified migraine subtype and the absence of significant comorbidities, ensuring a generally healthy cohort. Lifestyle considerations included adherence to the contraception requirement; no additional restrictions on diet or physical activity were stipulated. The sponsor did not provide information on the total number of participants.

The study employs a randomized, double-blind, placebo-controlled parallel‑group design to evaluate the ability of a single oral dose of apremilast 30 mg to induce migraine in women with a history of Migraine without aura. After an initial screening visit to confirm eligibility, participants receive either the test medication or lactose monohydrate under blinded conditions and are observed for up to 12 hours post‑administration. Vital signs, headache characteristics, and adverse events are recorded at predefined time points, including a 90‑minute assessment of heart rate and mean arterial pressure. The primary efficacy assessment is the primary endpoint defined as the difference in the occurrence of migraine‑like attacks between the two arms during the observation period. Secondary assessments include headache intensity over time, occurrence of any headache, hemodynamic changes, and safety events. Participant involvement spans approximately one day, encompassing the screening, dosing, and end‑of‑study assessments; follow‑up contacts may be performed to capture delayed adverse events. Early termination may occur if a participant experiences a serious adverse event, withdraws consent, fails to comply with study procedures, or is found to be ineligible after screening.

The investigational product is apremilast supplied as Apremilast STADA 30 mg film‑coated tablets. The medication is administered orally as a single dose of one 30 mg tablet, taken with water under fasting conditions. The route of administration is oral, and the dosing frequency is a one‑time administration for the purpose of assessing acute effects.

The comparator in the study is an inert placebo consisting of lactose monohydrate. The placebo is presented in a tablet form matching the appearance of the active drug and is taken orally in a single dose identical in timing and conditions to the investigational product.

All participants receive the assigned tablet in the clinic under direct observation to ensure compliance with the dosing schedule. Study staff record the exact time of ingestion and monitor participants for a predefined observation period to capture any symptomatic responses. Compliance is verified by confirming tablet consumption and documenting any deviations from the protocol.

Efficacy will be assessed by comparing the occurrence of migraine-like attacks between participants receiving apremilast and those receiving placebo during the entire observational period, defined as the 12‑hour interval following a single oral dose.

Secondary efficacy evaluations include analysis of headache intensities over time within the same 12‑hour window, assessment of the occurrence of any headache irrespective of migraine criteria, measurement of heart rate and mean arterial pressure up to 90 minutes post‑administration, and comparison of the incidence of adverse events throughout the 12‑hour observation period.

All endpoints will be captured using standardized recording procedures at predefined time points: continuous monitoring for cardiovascular parameters during the first 90 minutes and periodic symptom assessments up to 12 hours. Data will be analyzed to determine differences between the apremilast and placebo groups for each specified endpoint.