Effect of Intranasal Oxytocin on Headache in Chronic Daily Headache

The TI004 and TI005 studies both used a randomized, double-blind, placebo-controlled, parallel-group study design. A protocol-specified interim analysis was performed after completion of the first 40 subjects, resulting in termination of the TI004 study and development of the TI005 protocol, which included the following changes from the TI004 protocol:

• Increase in oxytocin dose from 32 to 64 IU;
• Extension of the in-clinic observation period from 2 hours post-dose to 4-hours post-dose;
• Reduction in sample size from 40 to 20 subjects;
• Elimination of the laboratory measurements during the screening visit, allowing V1 and V2 potentially to be combined, expediting study completion;
• Adding in-clinic observation and assessment at 3 hours and 4 hours post-dose and out-of-clinic assessment at 8 hours post-dose.

The primary outcome measure is the reduction in headache intensity after drug administration; secondary outcome measures are the headache symptoms, nausea, vomiting, photophobia, and phonophobia. Additional secondary outcome measures are intake of rescue medication and patient satisfaction over a period of 24 hours.

Inclusion criteria

• Headache on equal to or more than 15 days per month for at least 6 months; the headaches can be migraine or tension.
• More than half of the monthly headaches are of moderate or severe intensity on the 4-point categorical pain rating scale and are assessed as 6 or higher on the 11-point numerical pain rating scale.
• Headaches typically last for at least 4 hours.
• Subjects are on a stable headache treatment, if any, for at least 2 months.

Exclusion criteria

• Headache symptoms assessed to be predominately occipital.
• Allergy to oxytocin.
• History of addictive behavior (e.g. alcoholism, drug abuse).
• History of significant psychiatric disorder.
• History of clinically-significant, functionally-impairing cardiovascular or pulmonary disease.
• Upper-respiratory tract infection at the time of randomization.
• Past or current history of any condition that may hinder study procedures or confuse interpretation of data.
• Nasal obstruction of any cause as determined at screening.
• Major surgery or trauma within 4 weeks of screening.
• Women who are pregnant as evidenced by a serum HCG, nursing, or trying to conceive.
• Use of intranasally administered medications, for example, vasoconstrictors or corticosteroids, within 2 weeks of randomization.
• Use of an investigational medication or device within 30 days of randomization.
• Unable or unwilling to adhere to the study-specific procedures and restrictions.
• Any condition that in the opinion of the investigator would compromise the safety of the subject or the quality of the data.
• Alanine aminotransaminase (ALT) or aspartate aminotransaminase (AST) equal or greater than 3 times the upper limit of normal (ULN).
• Serum creatinine of equal or greater than 1.8 mg/dL. Resting, sitting systolic blood pressure equal or greater than 160 mmHg or diastolic blood pressure equal or greater than 100 mmHg at screening. For patients with previously diagnosed hypertension, antihypertensive medications must be stable for at least 30 days prior to screening.