A Phase I, Randomized, double-blind, placebo-controlled sequential study to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of ADX71441 after single oral ascending doses, and multiple oral ascending dose following a standard dose escalation schedule, randomized, double-blind for placebo and positive control, in normal healthy volunteers

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 150

Inclusion Criteria

1. Willing and able to provide written informed consent,
2. Male healthy volunteers 18 to 55 years of age,
3. Subjects with a weight of 75 ±15 kg at screening,
4. In good health as determined by medical history and physical examination,
5. Able to communicate well with the Investigator and research staff and willing and able to comply with all study procedures and visits,
6. Normal arterial blood pressure (BP) and pulse rate or, if abnormal, considered not clinically significant by the Principal Investigator (PI) and MM,
7. Negative test for selected drugs of abuse at the Screening visit,
8. Negative test for alcohol use (breathalyzer) at the Screening visit.

Exclusion Criteria

1. Who has a positive hepatitis panel (including hepatitis B surface antigen [HBsAg] and hepatitis C virus antibody [anti-HCV]), or a positive HIV antibody screen,
2. Who previously received ADX71441,
3. Who present with acute or chronic or history of symptoms of gastrointestinal disturbances (GI) or on physical examination have evidence of any clinical signs of acute or chronic GI abnormality (i.e. hemorrhoids, GI bleeding, etc.),
4. Who have a history of chronic uncontrolled medical conditions that may cause a medical emergency in the case of a provoked seizure,
5. Who presents with any clinical abnormality identified during pre-study laboratory tests, full physical examination, vital signs, and ECG, unless deemed acceptable by the PI and the Sponsor,
6. Who present with a diagnosis of epilepsy or history of seizures or fainting spells of unknown or undetermined etiology or has a family history of treatment resistant epilepsy,
7. Who present with or have a history of progressive neurological disorder or focal signs of abnormality on neurological examination,
8. With any history of abnormal EEG or EEG signal suggesting a possible risk of epilepsy, febrile convulsions, etc.,
9. Who present with a history of schizophrenia, bipolar disorder, or other psychotic disorder as defined by DSM-IV_TR,
10. Who have a history of moderate to severe depression, or suicide ideation,
11. Who have a history of allergy, intolerance or photosensitivity to any drug, or who have a history of serious allergy, asthma, allergic skin rash or sensitivity to any drug,
12. Who have a current or recent history (within 6 months of screening) of drug or substance abuse, including alcohol (>= 14 units per week), or who have a significant history of alcoholism or drug/chemical abuse within 6 months prior to the Screening visit (one unit of alcohol equals * pint [285 mL] of beer or lager, one glass [125 mL] of wine, or one shot [25 mL] of spirits),
13. Who drink more than 8 cups daily of beverage containing caffeine,
14. Who currently smoke or have used tobacco products (or equivalent) within 2 weeks prior to the screening visit,
15. Who have undergone surgery or have donated blood within 12 weeks prior to the start of the study,
16. Who currently use any prescription medications/products (with the exception of prescription medications deemed acceptable by the Investigator and Sponsor),
17. Use of any over the counter (OTC), non-prescription preparations (including vitamins, minerals, phytotherapeutic/herbal/plant-derived preparations) within 14 days prior to the Check-in visit, unless deemed acceptable by the Investigator and Sponsor,
18. Who have any clinical condition or prior therapy which, in the opinion of the Investigator, make the subject unsuitable for the study , could compromise subject safety, limit the subject*s ability to complete the study, and/or compromise the objectives of the study,
19. Who have participated to any clinical trial with an investigational drug in the past 3 months preceding study entry,
20. Who have a history of a clinically significant cardiac disease (e.g., myocardial infarction or stroke within 6 months prior to Screening unstable angina, claudication, etc.), or evidence of a clinically significant electrocardiogram (ECG) abnormality at Screening,
21. Who have a history of orthostatic hypotension or evidence orthostatic hypotension at Screening,
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Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Plasma drug concentration of ADX71441 (pharmacokinetics)<br /><br><br /><br>Pharmacodynamic evaluation (PD):<br /><br>- Smooth pursuit,<br /><br>- Saccadic eye movements,<br /><br>- Adaptive tracker,<br /><br>- Body sway,<br /><br>- VAS (Bowdle, Bond & Lader)<br /><br>- Learning Maze Task,<br /><br>- Simple Reaction time task,<br /><br>- Stop Signal task,<br /><br>- Visual Verbal Learning Task.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Safety parameters:<br /><br>- Vital signs (BP [standing and lying], HR, RR, Temperature),<br /><br>- Clinical laboratory: Hematology and Chemistry,<br /><br>- ECG (holter),<br /><br>- EEG.<br /><br><br /><br>Adverse events during the trial (AEs).<br /><br><br /><br>Concomitant medication.<br /><br><br /><br>Growth Hormone (GH) plasma concentrations.</p><br>