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| Horai Pharmaceutical, Co., Ltd. Protocol for a fictitious “Hangover-alleviating agent” Protocol Number: HORAI-2DAYS401 Version 2: Date of revision: August 11, 2004 Revisions: The following items have been added: #1; Presumed raw material #2; Considerations for manufacturing #3; Implications for the development of this study drug #4; Stability |
| Synopsis of the study drug The mechanism of the study drug is activation of acetaldehyde dehydrogenase (ALDH). Two types of ALDH have been identified: ALDH2 that is active at lower concentrations of acetaldehyde and ALDH1 that is active only at higher acetaldehyde concentrations. Approximately half of the Japanese have weakly active or defective ALDH2 variants by nature. This type of individuals poorly tolerate alcohol by constitution and tend to get sick from drinking, even with a small amount of alcohol, because these isoenzymes fail to rapidly metabolize toxic acetaldehyde, a degradation product of alcohol. Thus, the drug is expected to act by activating the ALDH2 subtype. The drug product should be orally active with characteristics between a protein formulation and a low-molecular weight compound. Although not definitely confirmed, the drug substance may be pure water or ice with a specific wave motion, which derives from a luscious voice of a sweetheart. Considerations for manufacturingA voice of a good old wife may not be used to produce therapeutic wavelengths. Implications for the development of the study drugTo pioneer a new approach to tailor-made therapy Stability of the study drugIt may depend on a sweet relationship. Inclusion criteria (requirement for enrollment)1. During the two-month period just before enrollment, subjects have to have taken at least three sick leaves in the morning because of hangover. 2. Subjects have to be 20 years of age or older when providing informed consent (Rationale: the legal drinking age is 20 years). 3. Subjects have to have liver function test results that are less than or equal to twice the upper limit of normal. 4. Subjects have to prefer alcohol to three regular meals. Exclusion criteria (conditions that exclude potential participants from study enrollment)1. Individuals who cannot stay sober while receiving instructions along with the patient information sheet. 2. Individuals who are unlikely to practice contraception during the study. 3. Individuals who cannot drink alcohol. Target disease Hangover associated with headache, nausea, vomiting, and tinnitus These conditions should meet the following: 1. Blood alcohol concentrations of at least 0.03% or breath alcohol concentrations of at least 0.15 mg/L, as determined 6 hours after drinking or later2. Headache for which patients are inclined to take sick leave3. Nausea for which patients are inclined to face away from their supervisors, or vomiting on thinking of their supervisors4. Tinnitus for which patients cannot answer business calls Primary endpoints (outcome measures used to assess the efficacy of the drug) 1. The number of morning sick leaves taken with a poor excuse during the two-month study period 2. The frequency of nausea (according to the following criteria) (1) Nausea always occurs at the sight of the supervisor. (2) Nausea occurs at least once every two times of seeing the supervisor. (3) Nausea occurs at least once every five times of seeing the supervisor. (4) Nausea usually occurs at the sight of supervisor. Secondary endpoints (outcome measures used to indirectly assess the efficacy of the drug) 1. The number of drinking parties to attend (according to the following criteria) (1) Increased from once to thrice weekly (2) Increased from once to twice weekly (3) Seven times weekly 2. The rate of answering business calls (according to the following criteria) (1) Never answer any of five calls (2) Answer at least two out of five calls (3) Answer at least three out of five calls (4) Pick up the phone only to transfer all calls to the general affairs division after saying, “I will transfer your call to the department in charge.” Criteria for assessment An integrated assessment system with “drinking index” and “hangover index” proposed by the Japan Clinical Hangover Association (Geroppa Version 2.0) #1; Drinking index: alcoholicity×alcohol consumption×alcohol coefficient #2; Alcohol coefficients: 1 for distilled liquor (such as distilled spirit and whisky), 1.3 for brewage (such as sake, wine, and beer) #3; Hangover index is obtained by scoring above-mentioned variables. In the Sixth International Conference on Harmonisation (ICH-6) held in Osaka, however, the substantial difference in ALDH2 activity among races led to disagreement between Japan and Russia, resulting in failure of this index to progress to Step 2. Disallowed concomitant medication Hair of the dog |