An open-label, multiple dose study to compare the single-dose and steady-state pharmacokinetics of a 40 mg PHA-022121 extended-release (XR) tablet administered once daily between healthy Japanese, Chinese, and Caucasian volunteers.

Inclusion Criteria55

• Subject must sign an ICF indicating that the subject understands the purpose of the study
• including the procedures required, potential risks involved, and is willing to participate in the study before starting any screening activities.
• Subject must be healthy, between 18 to 65 years of age (inclusive)at the time of informed
• consent.
• Subject must have a body mass index (BMI; weight in kg divided by the square of height in meters) between 17.0 and 32.0 kg/m2, extremes included, and a body weight between 45.0 kg and100.0 kg (inclusive), at screening
• A female subject may be enrolled if she is willing and able to adhere to the contraceptive
• requirement as follows:
• documented to be surgically sterile or postmenopausal: Permanent sterilisation methods
• include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
• practicing true abstinence for at least 21 days prior to dosing and until 90 days after study
• drug administration. The reliability of sexual abstinence needs to be evaluated if it is the
• preferred and usual lifestyle of the subject.
• using two forms of medically acceptable and effective contraception:
• where one should be a highly effective method such as a hormonal method (e.g.,
• contraceptive implants, injectables, oral contraceptives), or a non-hormonal method
• (e.g., intrauterine device), from Screening or at least 2 weeks prior to study drug
• administration (whichever is earlier) until 90 days after the study follow-up visit,
• and the other should be a physical barrier method.
• Notes
• Two forms of above-mentioned contraception are not needed if the male partner is
• sterilized.
• Contraception is not needed for same-sex contacts.
• All female subjects must have a negative serum ß-human chorionic gonadotropin (ß-hCG)
• pregnancy test at Screening and at Day -1 of each treatment period.
• Subject must be willing and able to adhere to the prohibitions and restrictions as follows:
• Subject must remain at the clinical site throughout the study duration.
• Within 7 days before first study drug administration and throughout the study, the use of prescription and nonprescription medication (including vitamins and herbal supplements) other than the study drug are prohibited.
• The use of paracetamol is allowed up to 72 hours prior to the first study drug administration (Day 1). After that and at the discretion of the Investigator, a maximum of 1000 mg dose per day paracetamol, will be allowed for the treatment of headache or other pain.
• The use of hormonal contraceptives or hormonal replacement therapy is allowed for female subjects of child-bearing potential or post-menopausal respectively.
• Subject must not consume food or beverages containing alcohol or quinine (e.g., tonic water, bitter lemon, etc.) from 48 hours prior to admission to the clinical site and during clinical site confinement.
• Subject must not consume grapefruit or grapefruit juice, pomelo juice, star fruit, or Seville orange products starting from 72 hours before the first PK sample is drawn and during clinical site confinement.
• Subject must refrain from any methylxanthine containing products, (e.g., chocolate bars or chocolate beverages, coffee, teas, colas, etc.) from 48 hours before administration of study drug and during clinical site confinement.
• Subjects are advised not to consume food containing poppy seeds or codeine starting 72 hours before screening or 72 hours before admission to clinical site (in order to avoid false positive urine drug test).
• Subjects must consume standard institutional meals during confinement to the clinical site. Excessive food consumption will not be permitted.
• Subjects must refrain from the use of nicotine-containing substances, including tobacco products (e.g., cigarettes, e cigarettes, cigars, chewing tobacco, gum, or patch) while confined to the clinical site.
• If a subject has had a febrile illness 5 days before the first study drug administration, the first administration of study drug should be postponed until body temperature has been normalized for at least 72 hours.
• Subjects should avoid strenuous exercise (e.g., long distance running equal to 5 km/day, weight-lifting, or any physical activity to which the subject is not accustomed) and sunbathing from 96 hours before admission to the clinical site and while confined to the clinical site.
• Subjects must avoid donating blood for at least 60 days after completion of the study and are advised not to participate in an investigational drug study for at least 30 days after completion of the study.
• A female subject may be enrolled if she is willing and able to adhere to the contraceptive requirement as specified as follows:
• documented to be surgically sterile or postmenopausal: Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
• practicing true abstinence for at least 21 days prior to dosing and until 90 days after study drug administration. The reliability of sexual abstinence needs to be evaluated if it is the preferred and usual lifestyle of the subject.
• using two forms of medically acceptable and effective contraception:
• where one should be a highly effective method such as a hormonal method (e.g., contraceptive implants, injectables, oral contraceptives), or a non-hormonal method (e.g., intrauterine device), from Screening or at least 2 weeks prior to study drug administration (whichever is earlier) until 90 days after the study follow-up visit,
• and the other should be a physical barrier method.
• Notes:
• Two forms of above-mentioned contraceptions are not needed if the male partner is sterilized.
• Contraception is not needed for same-sex contacts.
• Subject must be healthy on the basis of a medical evaluation that reveals the absence of any
• clinically relevant abnormality at screening per Investigator discretion.
• Cohort 1: Japanese subjects (in addition) defined as follows
• Japanese subjects are defined as first- or second- or third-generation Japanese of full Japanese parentage. No specific distribution among the generations is required.
• Cohort 2: Chinese subjects (in addition) defined as follows
• Chinese subjects are defined as first- or second- or third-generation Chinese of full Chinese parentage. No specific distribution among the generations is required.
• Cohort 3: Caucasian subjects (in addition)
• Subjects must be Caucasian, which is identified as of European, Middle Eastern, or North African descent.