Drug Development Program2

Drug Development Program

(Overview of what we are doing, and what has already been done)

Preclinical development in repurposing LAT8881 for treatment of Osteoarthritis.

Preclinical Safety and Toxicity

The safety and toxicity of LAT8881 has been evaluated using conventional repeat-dose studies of administering the active substance into animal models.

  • Effects were monitored on food consumption, ability to gain weight normally, haematology, blood and urine biochemistry, local reaction, cardiovascular, gastrointestinal (GI) tract and respiratory pharmacology and macroscopic and microscopic examination of organs and tissues after sacrifice.
  • Studies have also been performed to ascertain that LAT8881 does not have significant potential to cause mutation or chromosomal damage in a conventional battery of test assays.

A Phase IIa Proof of Concept study LAT-NP-001 is currently underway using twice daily delivery of of 30mg of LAT8881 by capsule for the treatment of the painful symptoms of post herpetic neuralgia and diabetic neuropathy. Lateral Pharma is looking for efficacy at least comparable to Gabapentanoids and clinical safety comparable to prior clinical studies with LAT8881.

LAT-NP-001 started in March 2019 at four Australian sites: Melbourne, Sydney, Brisbane and Newcastle, while two UK sites are to commence upon regulatory approval by July 2019.

The clinical trial protocol was developed by Lateral’s in-house team, with input from the clinical advisory board and experienced clinicians including Prof Paul Rolan, Prof Ralf Baron, Prof Tony Pickering and Prof Andy Rice

A Phase I study was conducted in 2001 (METAOD001). LAT8881 was administered intravenously to 14 healthy male volunteers.

  • LAT8881 was well tolerated over the dose range.
  • There were no clinically significant adverse events (AEs); or significant abnormalities in vital signs, safety laboratory tests or electrocardiograms (ECGs) during the study.
  • The safety profile of LAT8881 was similar to that seen with the positive control, rhGH, as well as placebo.

At the end of 2001 the first Phase IIa study was completed (METAOD002). This was a double-blind placebo-controlled 4 x 4 Latin Square design study in which 24 healthy clinically obese males participated.

  • LAT8881 was well tolerated over the dose range: there were no study drug-related withdrawals, serious AEs, clinically significant AEs, or changes of clinical significance in vital signs, safety laboratory tests, or ECGs during the study.
  • Significant differences in NEFA levels were observed 2 hours following administration of LAT8881 25 µg/kg and 100 µg/kg compared with placebo.
  • No significant changes in glucose or insulin-like growth factor 1 (IGF-1) levels were observed following LAT treatment compared with placebo.

A second double-blind placebo-controlled 4  4 Latin Square design Phase IIa study was conducted using single oral doses to evaluate safety, tolerability and pharmacodynamic endpoints in healthy, clinically obese males (METAOD003).

  • LAT8881 was well tolerated over the oral dose range: there were no study drug-related withdrawals or serious AEs, clinically significant AEs, or changes of clinical significance in vital signs, safety laboratory tests or ECGs during the study.
  • The levels of NEFA were statistically significantly increased compared to placebo 4 hours following administration of LAT8881.
  • No significant differences in IGF-1 values were evident for any of the doses compared to placebo.
  • A trend in the Nottingham Health Profile scores (a questionnaire-based measure of general well-being) was noted in all treated groups compared to placebo. There was an increase in sense of well-being reported one week after dose, with the greatest effect observed at 27 mg.

A third Phase IIa study was conducted to assess the safety of multiple daily oral dosing of LAT8881(METAOD004).

  • LAT8881 was well tolerated over the oral dose range: there were no study drug-related withdrawals or serious AEs, clinically significant AEs, or changes of clinical significance in vital signs, safety laboratory tests or ECGs during the study.
  • Trends were observed with body weight data in that subjects who received LAT8881 9 mg and 27 mg lost more weight at the end of the treatment period than those who received placebo, a difference which was maintained one week later.

A Phase IIb study was conducted to determine whether LAT8881 caused a reduction in body weight or body fat following daily dosing (capsule formulation) for 12 weeks (METAOD005). The patients were clinically obese males, and females of non-child bearing potential.

  • LAT8881 was well tolerated over the dose range; there were no changes of clinical significance in vital signs, safety laboratory tests or ECGs during the study.
  • The primary endpoint of mean weight loss over 12 weeks was greater in all LAT8881 treatment groups compared to placebo, with a non-linear bimodal dose response.
  • Repeated measures analysis of the mean weekly rate of weight loss over the 12 weeks with LAT8881 at doses of 1 mg (-0.22 kg/week, p < 0.0001), 20 mg (-0.13 kg/week, p = 0.0451), or 30 mg (-0.15 kg/week, p = 0.0107) was significant compared to placebo (-0.07 kg/week). The mean weekly rate of reduction in abdominal circumference was also significant at all doses of LAT8881 compared to placebo (p range of < 0.0001 to 0.01).
  • This study demonstrated that daily oral administration of LAT8881 was safe and well tolerated and promoted weight and waistline reduction. The dose-response relationship is complex, with both low dose and high dose effects and differential effects at high doses between men and women.

The OPTIONS Study was a Phase IIb, randomised, double-blind, placebo-controlled, multicentre, parallel-group study to assess the efficacy, safety, and tolerability of 24 weeks of treatment with different doses of LAT8881 tablets for weight loss in obese adults (METAOD006). A total of 413 subjects contributed to the primary analysis.

Overall, results after 24 weeks of double-blind treatment indicated that differences in weight change among the randomised treatment groups were not statistically significant (p=.34863).

As a result, the obesity program was terminated in February 2007.