An Open Label Study to Evaluate the Pharmacokinetic Exposure of Apremilast in Healthy Subjects
| Status: | Completed |
|---|---|
| Conditions: | Healthy Studies |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | 18 - 55 |
| Updated: | 11/24/2018 |
| Start Date: | August 17, 2016 |
| End Date: | November 22, 2016 |
A Phase 1, Open Label, Randomized, Two Part Study to Evaluate the Pharmacokinetic Exposure of a Once-Daily (QD) Apremilast Formulation Relative to the Twice-Daily (BID) Reference Immediate Release (IR) Tablet and the Effect of Food on the QD Apremilast Formulation in Healthy Subjects.
This study will be conducted in 2 Parts. The purpose of this study is to measure how much of
apremilast is found in the blood when administered as a once daily tablet compared to a twice
a day tablet, when given as multiple doses (Part 1) and when administered as a single dose
under fasting and fed conditions (Part 2). Information on the safety and tolerability of
apremilast will also be obtained. In addition, the effect of apremilast on certain biomarkers
in the blood will be evaluated in 16 assigned subjects (Part 1 only). Biomarkers are
substances such as proteins that tell us how the study drug is working in your body.
Part 1: This is a multi-center, phase 1, open-label, randomized, two-period, two-sequence,
crossover study in healthy subjects. The study will consist of a screening phase, a baseline
phase, two treatment periods, and a follow-up phone call. Each Period will be ten days in
duration (Day 1 through Day 10) for dosing and sample collection for up to 72 hours post Day
7 morning dose of Periods 1 and 2. There will be a washout between Period 1 and Period 2.
Part 2: This is a single center, open-label, randomized, four-period, four-sequence crossover
study to evaluate the PK and exposure of apremilast following single dose administration of
different formulations of apremilast. Part 2 will consist of a Screening phase, Baseline,
four Treatment periods, and a follow-up phone call. Each Period will be four days in duration
(Day 1 through Day 4) for dosing and sample collection for up to 72 hours post Day 1 of
Period 1, 2, 3, and 4.
apremilast is found in the blood when administered as a once daily tablet compared to a twice
a day tablet, when given as multiple doses (Part 1) and when administered as a single dose
under fasting and fed conditions (Part 2). Information on the safety and tolerability of
apremilast will also be obtained. In addition, the effect of apremilast on certain biomarkers
in the blood will be evaluated in 16 assigned subjects (Part 1 only). Biomarkers are
substances such as proteins that tell us how the study drug is working in your body.
Part 1: This is a multi-center, phase 1, open-label, randomized, two-period, two-sequence,
crossover study in healthy subjects. The study will consist of a screening phase, a baseline
phase, two treatment periods, and a follow-up phone call. Each Period will be ten days in
duration (Day 1 through Day 10) for dosing and sample collection for up to 72 hours post Day
7 morning dose of Periods 1 and 2. There will be a washout between Period 1 and Period 2.
Part 2: This is a single center, open-label, randomized, four-period, four-sequence crossover
study to evaluate the PK and exposure of apremilast following single dose administration of
different formulations of apremilast. Part 2 will consist of a Screening phase, Baseline,
four Treatment periods, and a follow-up phone call. Each Period will be four days in duration
(Day 1 through Day 4) for dosing and sample collection for up to 72 hours post Day 1 of
Period 1, 2, 3, and 4.
Study Objectives
Part 1 Primary Objectives To evaluate the pharmacokinetics (PK) and exposure of apremilast
following multiple-dose administration of a QD apremilast formulation relative to the BID
reference IR tablet under the fed condition with a standard meal.
Secondary Objectives To evaluate the safety and tolerability of a QD apremilast formulation
and the BID reference IR tablet.
Exploratory Objective To evaluate the pharmacodynamics (PD) of apremilast following
multiple-dose administration of the QD apremilast formulation relative to the BID reference
IR tablet under the fed condition with a standard meal.
Part 2 Primary Objectives To estimate the PK and exposure of apremilast following single dose
administration of a QD apremilast formulation relative to the BID reference IR tablet under
the fasting condition To estimate the effect of food on the PK of a single oral dose of a QD
apremilast formulation.
Secondary Objectives To evaluate the safety and tolerability of a QD apremilast formulation
and the BID reference IR tablet.
Part 1 Primary Objectives To evaluate the pharmacokinetics (PK) and exposure of apremilast
following multiple-dose administration of a QD apremilast formulation relative to the BID
reference IR tablet under the fed condition with a standard meal.
Secondary Objectives To evaluate the safety and tolerability of a QD apremilast formulation
and the BID reference IR tablet.
Exploratory Objective To evaluate the pharmacodynamics (PD) of apremilast following
multiple-dose administration of the QD apremilast formulation relative to the BID reference
IR tablet under the fed condition with a standard meal.
Part 2 Primary Objectives To estimate the PK and exposure of apremilast following single dose
administration of a QD apremilast formulation relative to the BID reference IR tablet under
the fasting condition To estimate the effect of food on the PK of a single oral dose of a QD
apremilast formulation.
Secondary Objectives To evaluate the safety and tolerability of a QD apremilast formulation
and the BID reference IR tablet.
Inclusion Criteria:
Subjects must satisfy the following criteria to be enrolled in the study (Part 1 and Part
2):
1. Must understand and voluntarily sign a written Informed consent form (ICF) prior to
any study-related procedures being performed.
2. Must be able to communicate with the investigator, understand and comply with the
requirements of the study, and agree to adhere to restrictions and examination
schedules.
3. Male and female subjects of any race between 18 to 55 years of age (inclusive), and in
good health as determined by the Investigator at the time of signing the informed
consent document.
4. Have a body mass index (BMI) between 18 and 33 kg/m2 (inclusive).
5. No clinically significant laboratory test results as determined by the investigator.
6. At the screening visit, must be afebrile, with supine systolic BP: 90 to 140 mmHg,
supine diastolic BP: 50 to 90 mmHg, and pulse rate: 40 to 110 bpm. Eligibility
criteria for vital signs performed during check-in and/or predose on Day 1 will be at
the discretion of the Investigator.
7. Must have a normal or clinically acceptable 12-lead Electrocardiogram (ECG). Subjects
must have a QT interval corrected using the Fridericia formula (QTcF) value ≤ 450
msec.
8. Female subjects
1. Must have a negative pregnancy test
2. If postmenopausal: must have follicular stimulating hormone (FSH) test result >
40 IU/L and a negative pregnancy test
9. Contraception Requirements:
Must comply with the following acceptable forms of contraception. All Female of child
bearing potential (FCBP)1 must use one of the approved contraceptive options as
described below while taking apremilast and for at least 28 days after administration
of the last dose of the apremilast. At the time of study entry, and at any time during
the study when a FCBP's contraceptive measures or ability to become pregnant changes,
the Investigator will educate the subject regarding contraception options and the
correct and consistent use of effective contraceptive methods in order to successfully
prevent pregnancy.
All FCBP must have a negative pregnancy test at Screening and Day -1 of each Treatment
Period. All FCBP subjects who engage in activity in which conception is possible must
use one of the approved contraceptive options described below:
Option 1: Any one of the following highly effective methods: hormonal contraception
(oral, injection, implant, transdermal patch, vaginal ring); intrauterine device
(IUD); tubal ligation; or partner's vasectomy; OR Option 2: Male or female condom
(latex condom or non-latex condom NOT made out of natural [animal] membrane [for
example, polyurethane]); Plus one additional barrier(c) contraceptive sponge with
spermicide.
Male subjects (including those who have had a vasectomy) who engage in activity in
which conception is possible must use barrier contraception (latex or non-latex
condoms NOT made out of natural [animal] membrane [for example, polyurethane]) while
on Investigational Product (IP) and for at least 28 days after the last dose of IP.
10. Must agree to refrain from donating sperm, blood or plasma (other than for this study)
while participating in this study and for at least 28 days after the last dose of
investigational product.
11. Subject is willing and able to adhere to the study visit schedule and other protocol
requirements.
Exclusion Criteria:
The presence of any of the following will exclude a subject from enrollment:
1. History of any clinically significant and relevant neurological, psychiatric,
gastrointestinal, renal, hepatic, cardiovascular, psychological, pulmonary, metabolic,
endocrine, hematological, allergic disease, drug allergies, or other major disorders.
2. Any condition which places the subject at unacceptable risk if he were to participate
in the study, or confounds the ability to interpret data from the study.
1 A female of childbearing potential is a sexually mature female who 1) has not undergone a
hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical
removal of both ovaries) or 2) has not been postmenopausal for at least 24 consecutive
months (that is, has had menses at any time during the preceding 24 consecutive months).
3. Use of any prescribed systemic or topical medication within 30 days of the first dose
administration (exception, FCBP may use hormonal contraception).
4. Use of any non-prescribed systemic or topical medication (including vitamin/mineral
supplements, and herbal medicines) within 14 days of the first dose administration.
5. Any surgical or medical condition possibly affecting drug absorption, distribution,
metabolism and excretion, eg, bariatric procedure, colon resection, irritable bowel
syndrome, Crohn's disease, etc. Subjects with cholecystectomy and appendectomy may be
included.
6. Exposure to an investigational drug (new chemical entity) within 30 days prior to the
first dose administration or 5 half-lives of that investigational drug, if known (whichever
is longer). 7. Donated blood or plasma within 8 weeks before the first dose administration
to a blood bank or blood donation center.
8. History of drug abuse (as defined by the current version of the Diagnostic and
Statistical Manual [DSM]) within 2 years before dosing, or a positive drug screen
reflecting consumption of illicit drugs.
9. History of alcohol abuse (as defined by the current version of the DSM) within 2 years
before dosing, or a positive alcohol screen.
10. Known to have hepatitis, or known to be a carrier of the hepatitis B surface antigen
(HBsAg) or hepatitis C antibody (HCV Ab), or have a positive result to the test for human
immunodeficiency virus (HIV) antibodies at screening.
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