Table 2 Summary of preclinical in vivo toxicology studies of AmyP53.
Study | Test system or animal species | Study design | Doses | Results |
|---|---|---|---|---|
Ref. B-03767 Safety pharmacology study for behavioural effects of AmyP53 using the primary observation (Irwin) in Sprague Dawley rats | Irwin test in rats GLP | Single intranasal administration of AmyP53 or reference item (Morphine 8 mg/kg) | 3 doses 0.5, 1 and 5 mg/kg body weight (BW) | AmyP53 did not induce any relevant neurologic adverse effects related with neuro-behavioural functions associated with excitation, sedation, stereotypy, motor-coordination, autonomic and pain |
Ref. 20230069SPCP Evaluation of effects on cardiac and respiratory functions in conscious rats following single intranasal administration | Evaluation of cardiac and respiratory functions and activity level analyzed by telemetry jackets on Wistar rats | Single intranasal administration of AmyP53 Recordings during a 24 h-period | 1 dose 5 mg/kg BW | AmyP53 administered by the intranasal route did not induce any statistically significant change on the cardiac and respiratory function, and activity level. |
Ref. AMYPORE/P3-T-0719/AmyP53/IV-IN/v1 Determination of the maximum tolerated dose of AmyP53 administered by intravenous and intranasal routes in rats | Assessment of the MTD of AmyP53 injected intravenously or intranasally in female Wistar rats GLP | Evaluation criteria: body weight, mean body weight change, behaviour and macroscopic autopsy of rats | Increasing doses ranging from 0.128 to 80 mg/kg BW (intravenous) or 0.0064 to 4 mg/kg BW (intranasal route) every two days between D1 and D9 | The maximal tolerated dose (MTD) of AmyP53 in female Wistar rats is greater than 80 mg/kg for the intravenous route and greater that 4 mg/kg BW for the intranasal route. |
Ref. AMYPORE/P4-T-0919/AmyP53/DRF-IN/v1 Determination of the dose range finding of AmyP53 administered by intranasal route in rats | Assessment of the DRF of AmyP53 injected intranasally in male and female Wistar rats GLP | Evaluation criteria: body weight, mean body weight change, food consumption, hematology, coagulation time, blood chemistry, histological analysis of organs and macroscopic autopsy of behaviour of rats | 3 doses 0.2, 1 and 5 mg/kg BW every two days during five days | The maximal intranasal dose of AmyP53 without any signs of toxicity or dysfunction, is greater or equal to 5 mg/kg BW in both male and female Wistar rats. |
Ref. B-03766 28-Day repeated dose toxicity of the test item AmyP53 after intranasal administration to male and female rats | Toxicology and toxicokinetics studies of AmyP53 injected intranasally in male and female Sprague Dawley rats GLP | Evaluation criteria: observation of local reaction, mortality, systemic clinical signs, body weight and food consumption, clinical pathology determinations, ophthalmic exams, organ weight, hematology, histopathological evaluation of a full list of tissues. | 3 doses 0.2, 1 and 5 mg/kg BW every day for 28 days followed by 14 days of recovery | The intranasal no-observed adverse effect level (NOAEL) was established at the highest actual dose level tested, 5 mg/kg BW/day |
Ref. 23P0122 14-Day repeated tolerability/toxicity study in rabbits by intranasal route with a 14-day recovery period and toxicokinetics | Toxicology and toxicokinetics studies of AmyP53 injected intranasally in male and female New Zealand White rabbits GLP | Evaluation criteria: observation of local reaction, mortality, systemic clinical signs, body weight and food consumption, clinical pathology investigations, ophthalmoscopy, organ weight, hematology, coagulation, clinical chemistry, histopathological evaluation of a full list of tissues. | 3 doses 0.2, 1 and 5 mg/kg BW every day for 28 days followed by 14 days of recovery | AmyP53 did not induce toxicity and is well tolerated after repeated intranasal administrations in rabbits at dose levels of 0.1, 1 and 5 mg/kg BW/day, therefore the dose level of 5 mg/kg BW/day is considered the No Observed Adverse Effect Level (NOAEL). |
Ref. PCA-03 A-21001 Genotoxicity assay: Ames test following the OECD 471 | Genotoxicity Ames test | Bacterial Reverse mutation test following the OECD 471 and the ICH guideline S2 (R1) | 6 doses (4.69 to 150 µg) | AmyP53 did not cause a positive mutagenic response |
