A Relative Bioavailability Study of a Prasugrel Orally Disintegrating Tablet
Condition: Sickle Cell Disease
MeSH terms: Anemia, Sickle Cell
Intervention: Prasugrel (clinical formulation); Prasugrel (Orally Disintegrating Tablet [ODT])
Intervention description: Administered orally; Administered orally
Intervention MeSH terms: Prasugrel Hydrochloride
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This study compares the clinical tablet formulation of prasugrel taken orally with an orally
      disintegrating tablet (ODT) taken orally. The study will evaluate the amount of prasugrel
      active metabolite circulating in the blood for each treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Overtly healthy males or females, as determined by medical history and physical
             examination

          -  Are either women who are of child-bearing potential, surgically sterilised or defined
             as post-menopausal. Female subjects of child-bearing potential (not surgically
             sterilised between menarche and menopause) must have a negative pregnancy test at the
             time of screening and must be using a reliable method of birth control. These include
             tubal ligation, an intrauterine device which has been in place for at least 3 months,
             the oral contraceptive pill which has been taken, without difficulty, for at least 3
             months, or an approved hormonal implant. Barrier methods alone (condoms or
             diaphragm/cap) are not acceptable, but must be used in conjunction with a chemical
             method, that is, spermicidal gel. A woman is presumed to be post-menopausal if she has
             had amenorrhoea for greater than 12 months alone or amenorrheic for 6 to 12 months and
             has a serum oestradiol concentration <73 picomoles per liter (pmol/L) (20 picograms
             per milliliter [pg/mL]) (not applicable for women on hormone replacement therapy [HRT;
             oestrogen]) and a follicle stimulating hormone (FSH) concentration >40 international
             units per liter (IU/L).

          -  Have clinical laboratory test results within normal reference range for the
             investigator site, or results with acceptable deviations that are judged to be not
             clinically significant by the investigator

          -  Between the body mass index (BMI) of 18.5 and 32.0 kilograms per meter squared
             (kg/m^2), inclusive

          -  Have acceptable blood pressure (BP) and heart rate (HR) (supine) as determined by the
             investigator

          -  Have venous access sufficient to allow blood sampling

          -  Are reliable and willing to make themselves available for the duration of the study,
             and will abide by the research unit policy and procedure and study restrictions

          -  Have given written informed consent approved by Lilly and the Ethical Review Board
             (ERB) governing the site

        Exclusion Criteria:

          -  Have a history or presence of cardiovascular, respiratory, hepatic, renal,
             gastrointestinal, endocrine, haematological, or neurological disorders capable of
             significantly altering the absorption, metabolism, or elimination of drugs; of
             constituting a risk when taking the study medication; or of interfering with the
             interpretation of data, as determined by the investigator

          -  Evidence of significant active neuropsychiatric disease

          -  Have a history or presence of significant bleeding disorders, that is, haematemesis,
             melaena, severe or recurrent epistaxis, haemoptysis, haemorrhage, clinically overt
             haematuria, or intracranial haemorrhage

          -  Have a history (within the last 5 years) or presence of gastric ulcers. Previous
             history of duodenal ulcer is acceptable but must have been successfully surgically or
             medically treated with no further evidence of disease in the past 6 months (from
             screening)

          -  Have a personal or family history of coagulation or bleeding disorders or reasonable
             suspicion of vascular malformations, for example, cerebral haemorrhage, aneurysm, or
             premature stroke (cerebrovascular accident <65 years of age)

          -  Have a self-reported history of significant bleeding from trauma (for example,
             prolonged bleeding after tooth extraction)

          -  Are pre-menopausal females with a history or presence of menorrhagia within the last 5
             years (from screening)

          -  Have clinically significant out of range values for prothrombin time (PT), activated
             partial thromboplastin time (APTT), or platelet count at screening

          -  Have repeatedly reported positive results (at least 2 separate samples) on the faecal
             occult blood examination

          -  Have a history of major surgery within 3 months of screening

          -  Have planned surgery within 14 days after the last study day

          -  Have a clinically significant abnormality in fundoscopic examination or petechiae
             examination

          -  Have any other clinically significant abnormality following the investigator's review
             of the prestudy physical examination, electrocardiogram (ECG) and clinical (safety)
             laboratory tests

          -  Regularly use known drugs of abuse and/or show unacceptable positive findings on
             urinary drug screening

          -  Have known allergies or significant hypersensitivity to prasugrel or related drugs, or
             a history of relevant allergic drug reactions of any origin

          -  Have donated blood of more than 500 mL within the previous 1 month before prasugrel
             administration

          -  Show evidence of positive human immunodeficiency virus (HIV) antibodies

          -  Show evidence of positive hepatitis C antibody

          -  Show evidence of positive hepatitis B surface antigen

          -  Have a regular alcohol intake greater than 21 units/week for males or 14 units/week
             for females or are unwilling to comply with the alcohol consumption requirements from
             48 hours prior to the first dose of prasugrel until discharge from the clinical
             research unit (CRU) after the final Pharmacokinetics (PK) sample of Period 5 has been
             taken. One unit of alcohol is equal to 8 g ethanol

          -  Smoke 10 or more cigarettes per day

          -  Use prescription, over the counter or herbal medications that cannot safely be
             discontinued within 14 days prior to prasugrel administration. Exceptions: subjects
             may continue thyroid replacement therapy, HRT (oestrogen), contraceptives and certain
             medications that are inhaled or applied to the skin, eyes, or nose. The influenza
             vaccine may also be administered; however this must be at least 72 hours before any
             prasugrel dose

          -  Use proton pump inhibitors, antacids, or H2 antagonists, which may impact stomach pH

          -  Have participated in a study involving administration of an investigational compound
             within the 30 days prior to prasugrel administration

          -  Have any other condition that, in the opinion of the principal investigator increases
             the risk to the study subject or decreases the likelihood of obtaining reliable
             results from the study