Clinical Trials IHL-42X | Obstructive Sleep Apnoea (‘OSA’)
A novel cannabinoid formulated to moderate disordered sleeping and reduce OSA

OSA is an urgent health priority

OSA is estimated to affect almost 1 billion people worldwide and moderate to severe cases are a cause of significant patient suffering and substantial economic burden.

Disordered breathing during sleep leads to poor quality of sleep and decreased oxygen uptake. This leads to daytime sleepiness which negatively impacts productivity, mood and quality of life as well as increasing the risk of motor vehicle accident. Long term health effects of OSA include cardiovascular disease, cognitive impairments, diabetes and depression.

Incannex is pursuing an accelerated approval pathway for IHL-42X that will dramatically reduce the development time and time to registration and market exclusivity. The efficacy of IHL-42X will be assessed by measuring improvement in Apnoea Hypopnea Index (‘AHI’) and other symptoms of OSA in clinical trials.

  • OSA at affects up to 24% of men and 9% of women
  • Second most diagnosed respiratory condition after asthma
  • OSA is associated with a greater incidence of cardiovascular risk factors
  • Current treatment option (CPAP) proven to be poorly tolerated
  • Untreated OSA places a significant economic burden on the economy

Incannex has partnered with The Alfred Hospital in Melbourne to conduct a Phase 2b clinical trial to assess the efficacy of IHL-42X on Obstructive Sleep Apnoea (‘OSA’). Professor Terence O’Brien is the Principal Investigator; a world-renowned clinician and highly experienced Principal Investigator of more than 100 clinical trials. Professor O’Brien heads the Neuroscience Clinical Trials Unit at The Alfred Hospital and has an experienced team of study coordinators and research nurses. The primary endpoint of the clinical trial is the improvement in AHI as measured by an overnight polysomnography (‘PSG’) that will be assessed over multiple weeks.

Secondary outcomes include the following:

  • Reduction in oxygen desaturation index (‘ODI’)
  • Daytime somnolence measured by the Epworth Sleepiness Scale
  • Improvement in mood as measured by the POMS (Profile of Moods State), and well-being as measured by the Short Form 36
  • Safety of the IHL-42X combination will be established through adverse event monitoring.

The clinical trial protocol has been to be submitted to the Alfred Health Ethics Committee for review with comments and queries expected back from the ethics committee within the September quarter.

Incannex will endeavour to supply IHL-42X for sale in Australia under the Special Access Scheme for unregistered medicinal cannabis products, alongside its existing range of cannabinoid oils and CBD Inhaler. IHL will also proceed to the second Phase 2 ‘Factorial’ clinical trial as it compiles the necessary information for an FDA 505(b)(2) new drug application for exclusive marketability; details of which were released in the announcement on the 25th of March 2020 and entitled, “IHL-42X (OSA) accelerated FDA approval pathway”. Incannex has filed patents over the use of IHL-42X drug to be delivered to patient as a nocturnally administered pill to treat OSA.

OSA is a lethal disease that increases the risk of numerous health complications, affecting approximately 40M adults in the USA alone and causing an estimated economic burden in excess of $20B per annum. The main current treatment option is the mechanical CPAP device, however, patient compliance to CPAP devices has been proven low due to discomfort and claustrophobia. IHL anticipates greatly improved patient treatment compliance and outcomes from a once-nightly oral pharmaceutical product, such as IHL-42X, should it prove successful under clinical assessment.

What is Obstructive sleep apnea (OSA)?

What is Obstructive Sleep Apnoea?

Obstructive sleep apnoea (OSA) is a highly prevalent disorder, characterised by recurrent episodes of upper airway obstruction occurring during sleep, and associated with recurrent cycles of desaturation and re-oxygenation, sympathetic over-activity and intra-thoracic pressure changes, leading to fragmentation of sleep and consequent daytime fatigue and sleepiness. OSA is associated with decreased quality of life (QOL), significant functional impairment, and increased risk of road traffic accidents.

The condition is diagnosed based on data from an overnight sleep study where a measure called the apnoea-hypopnea index (‘AHI’) is calculated. Apnoea means a complete loss of breath for 10 seconds or longer. Hypopnea is a partial loss of breath that lasts 10 seconds or longer. The sleep tests will tell your doctor how many times each hour you have apnoea or hypopnoea.

An AHI >30 means that the patient’s condition is severe with more than 30 apnoeas and hypopnoeas per hour. Patients with severe OSA experience a greater incidence of cardiovascular risk factors.

Current treatment option (CPAP) proven to be poorly tolerated

What are the causes of Obstructive Sleep Apnoea?

Risk Factors of OSA

  • Excess weight. Most but not all people with obstructive sleep apnoea are overweight. Fat deposits around the upper airway may obstruct breathing.
  • Narrowed airway. You may inherit naturally narrow airways. Or your tonsils or adenoids may become enlarged, which can block your airway.
  • High blood pressure (hypertension). Obstructive sleep apnoea is relatively common in people with hypertension.
  • Chronic nasal congestion. Obstructive sleep apnoea occurs twice as often in those who have consistent nasal congestion at night, regardless of the cause. This may be due to narrowed airways.
  • Smoking. People who smoke are more likely to have obstructive sleep apnoea.
  • Diabetes. Obstructive sleep apnoea may be more common in people with diabetes.
  • Sex. In general, men are twice as likely as premenopausal women to have obstructive sleep apnoea. The frequency of obstructive sleep apnoea increases in women after menopause.
  • A family history of sleep apnoea. If you have family members with obstructive sleep apnoea, you may be at increased risk.
  • Asthma. Research has found an association between asthma and the risk of obstructive sleep apnoea.

Signs and Symptoms of OSA

  • Excessive daytime sleepiness and irritability
  • Loud snoring
  • Observed episodes of stopped breathing during sleep
  • Abrupt awakenings accompanied by gasping or choking
  • Awakening with a dry mouth or sore throat
  • Morning headache
  • Difficulty concentrating during the day
  • Experiencing mood changes, such as depression or anxiety
  • High blood pressure
  • Night sweating
  • Decreased libido

OSA with daytime sleepiness is estimated to affect 3% to 7% of men and 2% to 5% of women.

The prevalence of OSA at a treatable level is found to be about 24% in men and 9% in women aged 30-60 years of age. The prevalence of OSA with associated excessive daytime sleepiness is approximately 3% to 7% in adult men and 2% to 5% in adult women. Prevalence estimates do not vary significantly worldwide suggesting that OSA is as common in the developing world as in western society.

The CPAP Machine

Continuous Positive Airway Pressure (CPAP) machine, a machine that splints open the airway using air pressure delivered by a mask worn at night, is the gold standard for treatment of OSA.

CPAP is effective in reducing the severity of OSA and also reducing the incidence of the secondary complications of OSA such as MVAs, workplace accidents, coronary artery disease, stroke, diabetes.

However, long term compliance with CPAP has been shown to be poor with some papers suggesting almost 50% of people have abandoned treatment after only a short time due to:

• Noise and discomfort of apparatus

• Dislike of CPAP/difficult to use during travel

• Claustrophobia with mask

• Lack of affordability

• Complaints from spouses/partners