A multicentre, triple blind, placebo controlled, parallel group study of atorvastatin in episodic migraine (StatinMigEpisodic)

The primary objective of this study is to evaluate whether the favorable preventative effect of **atorvastatin** in two different doses, as observed in three smaller studies, can be confirmed in a larger multicenter randomized, controlled study. This is clinically relevant as it aims to establish the efficacy of atorvastatin in reducing the frequency of episodic migraine attacks, potentially offering a new therapeutic option for patients suffering from this condition.

Secondary objectives include assessing the number of responders to the treatment and evaluating the side effects associated with atorvastatin use. These objectives are crucial for understanding the overall benefit-risk profile of atorvastatin in the management of episodic migraine.

The clinical trial involves participants diagnosed with **migraine**, specifically targeting individuals aged 18 to 65 years who experience 4 to 14 migraine days per month. Both male and female subjects are included in the study, with no specific vulnerable populations being selected. Participants are required to have episodic migraine with or without aura, as defined by the ICHD-3 criteria, with the onset of migraine occurring at least one year prior to inclusion and before the age of 50. The study excludes individuals using other migraine prophylactics during the trial period. Women of child-bearing potential must not be pregnant or planning pregnancy during the study and are required to use highly effective contraception. The sponsor has not provided information regarding the total number of participants. The selection criteria ensure a focus on a population that can provide reliable data on the preventative effects of Atorvastatin in managing migraine symptoms.

The clinical trial is designed to evaluate the efficacy and safety of **atorvastatin** in the prevention of episodic migraine. This is a multicenter, triple-blind, placebo-controlled, parallel-group study. Participants will be randomly assigned to receive either atorvastatin 40 mg, atorvastatin 20 mg, or a placebo, administered orally in the form of film-coated tablets. The trial is expected to last until December 31, 2028, with recruitment anticipated to start on March 1, 2023. The study will include several key visits: an initial screening visit, multiple follow-up visits, and a final end-of-study visit. The screening visit will determine eligibility based on criteria such as age (18 to 65 years), frequency of migraine days (4-14 per month), and the absence of other migraine prophylactics. Follow-up visits will monitor the participants' response to the treatment, adherence to the protocol, and any adverse events. The end-of-study visit will assess the primary endpoint, which is the difference in the change from baseline in the number of migraine days per four weeks between the atorvastatin 40 mg group and the placebo group. Secondary endpoints include changes in the number of headache days and the number of responders with a ≥50% decrease in migraine days. Participant involvement is expected to last up to 12 months, with conditions for early termination including non-compliance with the study protocol, withdrawal of consent, or the occurrence of significant adverse events. The trial aims to confirm the preventative effects of atorvastatin observed in smaller studies, thereby contributing to the understanding of its role in migraine management.

The clinical trial involves the administration of **Atorvastatin** in two different dosages as the experimental medication. The first experimental treatment is **Atorvastatin Pensa 40 mg film-coated tablets**. This pharmaceutical form is designed for **oral use**. Participants will receive a maximum daily dose of one tablet, with a total maximum dose of 84 tablets over a treatment period of 12 weeks. The active substance, **atorvastatin**, is of chemical origin and is classified under the ATC code C10AA05. The medication is manufactured by Pensa Pharma AB and is not a paediatric formulation.

The second experimental treatment is **Atorvastatin Pensa 20 mg film-coated tablets**. Similar to the 40 mg dosage, this medication is also administered orally. Participants will receive a maximum daily dose of one tablet, with a total maximum dose of 84 tablets over a 12-week period. The active substance is the same, **atorvastatin**, and it is also of chemical origin, classified under the same ATC code. This formulation is also produced by Pensa Pharma AB and is not intended for paediatric use.

The study includes a **placebo** as a non-experimental treatment to serve as a comparator. The placebo is provided in the form of film-coated tablets and is administered orally. Participants in the placebo group will receive a maximum daily dose of one tablet, with a total maximum dose of 84 tablets over the same 12-week treatment period. The placebo tablets are designed to match the appearance of the active medication to maintain the study's triple-blind design.

Throughout the trial, participant compliance with the dosing schedule will be monitored to ensure adherence to the treatment protocol. The study aims to evaluate the preventative effects of atorvastatin in episodic migraine, comparing the outcomes of the two dosages against the placebo group.

The efficacy of **atorvastatin** in the treatment of episodic migraine will be assessed in a multicentre, triple-blind, placebo-controlled, parallel-group study. The primary endpoint for evaluating efficacy is the difference between the group receiving atorvastatin 40 mg daily and the placebo group in the change from baseline in the number of migraine days per 4 weeks. Secondary endpoints include the difference in change from baseline in the number of headache days per 4 weeks between the atorvastatin 40 mg group and the placebo group, as well as between the atorvastatin 20 mg group and the placebo group. Additionally, the number of responders, defined as participants experiencing a ≥50% decrease in migraine days compared with baseline, will be assessed between the atorvastatin 40 mg, atorvastatin 20 mg, and placebo groups.