Safety, Pharmacokinetics and Pharmacodynamics Study of Treatment With CHF 5074 in Healthy Young Male Subjects

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and tolerability of single oral doses of CHF 5074 in young healthy male volunteers.

Detailed Description
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The primary endpoint of the study is to determine the maximum tolerated dose (MTD) of CHF5074 after single oral administration to young healthy male volunteers. The secondary objective of this study is to evaluate the pharmacokinetics of CHF5074 after single oral administration to young healthy male volunteers. The secondary endpoint of this study is to verify if CHF5074 plasma levels (Cmax and AUC0-t) increase proportionally with the dose (dose-linearity). The exploratory objective of this study is to evaluate the pharmacodynamics of CHF5074 after single oral administration to young healthy male volunteers. The respective exploratory endpoint is to assess the relationship between individual maximum CHF5074 plasma concentrations and corresponding A-beta42 plasma concentrations corrected for baseline A-beta42 levels.

Official Title
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Placebo-Controlled, Ascending Single-Dose Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of CHF 5074 in Healthy Young Male Subjects

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Drug: CHF 5074
* Drug: placebo
* Drug: CHF 5074
* Drug: CHF 5074
* Drug: CHF 5074
* Drug: CHF 5074
* Drug: CHF 5074


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject's written informed consent is obtained prior to any study-related procedures. Subject is nonsmoking male between 18 and 45 years of age, inclusive. Subject has a body mass index between 18 and 30 kg/m2, inclusive. Subject is judged, by the investigator, to be in good health on the basis of medical history, complete physical examination including vital signs, 12-lead electrocardiogram (ECG) and standard laboratory tests including complete hematology, blood chemistry (glucose, creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, albumin, alkaline phosphatase, sodium, potassium), thyroid function, urinalysis (glucose, hemoglobin, blood, proteins, pH) and fecal occult blood. Subject understands the procedures and agrees to participate in the study program. Exclusion Criteria: Subject is mentally or legally incapacitated. Subject has a history of any illness that, in the opinion of the investigator and according to the protocol, might confound the results of the study or pose additional risk in administering CHF5074 to the subject. Subject has a medical history (within the last 10 years) of major cardiovascular, hepatic or renal disease. Subject has liver function test abnormalities with elevated AST or ALT greater than or equal to 2 times upper limit of normal and/or elevated bilirubin greater than or equal to 2 times upper limit of normal. Subject has renal function test abnormalities, including serum creatinine greater than 1.8 g/dL. Subject has abnormal fasting serum concentrations of TSH, T3 or T4. Subject has a positive result for fecal occult blood testing performed at screening. Subject has clinically significant abnormalities on physical examination, ECG or laboratory tests carried out at screening. Subject has a history of a psychiatric disorder. Subject has significant allergic conditions that require medical treatment or has known hypersensitivity to medications that could be activated by CHF5074 treatment. Subject is positive on testing for hepatitis B surface antigen, hepatitis C antibody or HIV 1 or 2 antibodies. Subject has donated blood within the 1 month prior to screening. Subject has a history of alcohol or drug abuse in the past 12 months. Subject used any psychoactive, recreational or prescription drug within the 4 weeks prior to study drug administration. Subject has used ibuprofen, sulindac sulfide, indomethacin, flurbiprofen within 2 weeks prior to study drug administration. Subject has used any other over-the-counter drug within 1 week prior to study drug administration Occasional treatment with acetaminophen or aspirin is permitted but must be reported to the investigator. Vitamins are permitted. Subject is positive on urine drug screening for drugs of abuse (cannabinoids, cocaine, opiates, amphetamines, barbiturates, benzodiazepines). Subject has evidence of alcohol on screening blood work and breathalyzer test. Subject does not agree to use a medically acceptable contraceptive (abstain from sexual intercourse, or use a condom with spermicide) for 7 days after study drug administration, or has not had a vasectomy at least 6 months prior to study participation. Subject is unlikely to comply with the study protocol or unable to understand the nature and scope of the study or the possible benefits or unwanted effects of the study treatments. Subject has participated in another investigational study within 30 days prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test Article<br> | Drug: CHF 5074<br>* 1x, oral capsule, single dose<br>Drug: CHF 5074<br>* 2x, oral capsule, single dose<br>Drug: CHF 5074<br>* 4x, oral capsule, single dose<br>Drug: CHF 5074<br>* 8x, oral capsule, single dose<br>Drug: CHF 5074<br>* 16x, oral capsule, single dose<br>Drug: CHF 5074<br>* 24x, oral capsule, single dose<br>|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* placebo, oral capsule, single dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events |  | from Screening through Day +3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose linearity of CHF5074 plasma levels (Cmax and AUC0-t) |  | Day -1 through Day +3 |