Zelira Therapeutics Ltd reported positive Phase 1b/2a results confirming that ZLT-101 therapy achieved the primary endpoint of a statistically significant improvement in Insomnia Severity Index (ISI) scores in patients diagnosed with chronic insomnia.

The Phase 1b/2a trial recruited 24 chronic insomnia patients, aged between 25-70. The study was a randomized, double-blind, cross-over design involving 14 nights of ZTL-101 and 14 nights of placebo, separated by a one-week washout period. All participants underwent a monitored sensitivity test to a mixture of ZTL-101 and placebo prior to commencing dosing. When dosing commenced each participant was able to take a single (0.5ml of 11.5mg total cannabinoids) or double (1 ml of 23mg total cannabinoids) dose of the medication, delivered sublingually, according to their symptoms.

Of the 23 participants who completed the protocol, 12 (52%) chose to increase the ZTL-101 medication from a single dose (0.5ml/11.5mg total cannabinoids) to double dose (1.0ml/23mg total cannabinoids) of ZTL-101 (as measured on the 14th night). Sixteen participants (69.5%) were taking a double dose (1.0ml) of the placebo on the 14th night.

The primary study endpoints were:

  1. safety of the medication based on adverse event reporting; and
  2. insomnia symptoms as measured by the Insomnia Severity Index (ISI) at the end of each of the 14 night active medication/placebo periods.

Primary Endpoint 1: Safe and Well Tolerated

A total of 36 non-serious adverse events possibly or likely related to ZTL-101 medication were recorded from 17 participants. The most frequently reported adverse event was xerostomia (dry mouth) (22.2% of all events) followed by dizziness (16.7%), headache (11.1%), and feeling abnormal (11.1%).

A total of 4 non-serious adverse events were recorded from 4 participants during dosing of the placebo medication. Headache was most frequently reported (50%) followed by dizziness (25%) and variable mood (25%).

All adverse events were classified as mild and had either resolved (97.5%) overnight or soon after waking each day or were resolving at the end of the trial.

Primary Endpoint 2: Significant Change in ISI Scores

Compared to baseline ISI scores (18.0±3.7) a significant decrease was observed following ZTL-101 (12.9±5.3, p<0.001) but not following placebo (18.0±4.3, p>0.05) (Figure 1 attached). The magnitude of decrease in ISI scores following ZTL-101 and placebo were 5.2±4.3 [Confidence Interval (CI) = 3.4 to 7.0] and 0.0±3.3 [CI = -1.8 to 1.9], respectively. The ISI scores following ZTL-101 and placebo were significantly different (p<0.001).

“This study represents the most rigorous clinical trial ever undertaken to assess the therapeutic potential of medicinal cannabis to treat the symptoms of chronic insomnia. It’s also the first trial to use the Insomnia Severity Index, arguably the current gold standard in this field, to measure the efficacy of a medicinal cannabis product to treat insomnia symptoms. The fact that ZLT-101 treatment achieved a statistically significant improvement in ISI scores is very impressive, particularly given the relatively short two-week dosing window. The lack of serious adverse or persistent mild adverse events is also encouraging given the reported safety issues for several already approved insomnia therapies. Taken together, these results suggest ZLT-101 has potential as a novel treatment for Insomnia.” says Peter Eastwood, principal investigator for the study, and director at the Centre for Sleep Science at the University of Western Australia, in a release.

Richard Hopkins, managing director ex-US markets, says, “We are delighted with the preliminary findings from this study. Additional analyses are ongoing and we expect to release a final report, including data from a comprehensive suite of secondary endpoints, by the end of March 2020 and thereafter, subsequent scientific publications based on the positive results from this study. We would like to acknowledge the dedicated team at the UWA Sleep Centre and express our gratitude to the patients and supporting investigators/organizations who participated in the study.”

Osagie Imasogie, chairman of Zelira, says, “The positive outcome to this trial represents an important milestone for Zelira and its commitment to address the unmet need for clinically validated cannabis medicines and offer more treatment options to physicians and patients. Having successfully completed its recent merger, Zelira is now poised to rapidly commercialize the world’s first clinically validated cannabis medicine for insomnia into global markets in 2020, including the US, based on the positive results of this study.”

Next Steps

A final report from the clinical study including an analysis of a comprehensive suite of secondary endpoints will be provided by end of March 2020. These results will inform the design of any future clinical studies.

Zelira will also seek to deploy its “Launch, Learn and Develop” strategy to commence supply of its clinically-validated insomnia formula in countries and states where medicinal cannabis has been legalized including Australia, the USA, Germany and the United Kingdom.