The purpose of this study is to assess the relative potency of multiple oral doses of LUM001
and SHP626 administered for 7 days as assessed by fecal bile acid excretion in overweight
and obese adult subjects. This study is designed to address the relative potency question
for the first time in the same.
1. An understanding, ability, and willingness to fully comply with study procedures,
study diet, and restrictions.
2. Ability to voluntarily provide written, signed, and dated (personally or via a
legally-authorized representative) informed consent/and assent as applicable to
participate in the study.
3. Aged 18-65 years inclusive at the time of consent. The date of signature of the
informed consent is defined as the beginning of the screening period. This inclusion
criterion will only be assessed at the first screening visit.
4. Males who agree to comply with any applicable contraceptive requirements of the
protocol or females of non-childbearing potential (see Section 4.4 for details).
5. Must be considered generally healthy. Health status is defined by the absence of
evidence of any active or chronic disease (see Section 184.108.40.206 for details and
exceptions) following the completion of a detailed medical and surgical history, a
complete physical examination, vital signs, 12-lead ECG, hematology, blood chemistry,
6. Must have a body mass index of 25.0-35.0 kg/m² inclusive with a body weight >63.5 kg
(140 lbs at the first screening visit). This inclusion criterion will only be
assessed at the first screening visit.
7. All clinical laboratory parameters are within normal laboratory limit or not found to
be clinically significant by the principal investigator.
8. Ability to swallow a dose(s) of investigational product(s).
1. History of any hematological, hepatic, respiratory, cardiovascular, renal,
neurological, or psychiatric disease, gall bladder removal, or current or recurrent
disease that could affect the action, absorption, or disposition of the
investigational product, or clinical or laboratory assessments.
2. Current or relevant history of physical or psychiatric illness, any medical disorder
that may require treatment or make the subject unlikely to fully complete the study,
or any condition that presents undue risk from the investigational product or
3. Known or suspected intolerance or hypersensitivity to the investigational product(s),
closely-related compounds, or any of the stated ingredients.
4. Significant illness, as judged by the investigator, within 2 weeks prior to the first
dose of investigational product.
5. Known history of alcohol or other substance abuse within the last year.
6. Donation of blood or blood products (eg, plasma or platelets) within 60 days prior to
receiving the first dose of investigational product.
7. Within 30 days prior to the first dose of investigational product:
- Have used an investigational product (if elimination half-life is <6 days,
otherwise 5 half-lives).
- Have been enrolled in a clinical study (including vaccine studies) that, in the
investigator's opinion, may impact this Shire-sponsored study.
- Have had any substantial changes in eating habits or exercise routine, as
assessed by the investigator
8. Confirmed resting systolic blood pressure >145 mmHg or <89 mmHg, and diastolic blood
pressure >95 mmHg or <59 mmHg.
9. Twelve-lead ECG demonstrating QTc >460 milliseconds for male subjects or >470
milliseconds for female subjects at screening. If QTc exceeds 460 milliseconds for
males or 470 milliseconds for females, the ECG should be repeated 2 more times and
the average of the 3 QTc values should be used to determine the subject's eligibility
10. A positive screen for drugs of abuse at screening or at Day -3 (check-in).
11. Male subjects who consume more than 21 units of alcohol per week or 3 units per day.
Female subjects who consume more than 14 units of alcohol per week or 2 units per
day. (1 alcohol unit=1 beer or 1 wine [5 oz/150 mL] or 1 liquor [1.5 oz/40 mL] or
0.75 oz alcohol).
12. A positive HIV, hepatitis B surface antigen (HBsAg), or hepatitis C virus (HCV)
13. Use of tobacco (eg, smoking or chewing) or other nicotine-containing products (eg,
gum, patch) in any form. Ex-users must report that they have stopped using tobacco
for at least 30 days prior to receiving the first dose of investigational product.
14. Routine consumption of more than 2 units of caffeine per day or subjects who
experience caffeine withdrawal headaches. (One caffeine unit is contained in the
following items: one 6 oz [180 mL] cup of coffee, two 12 oz [360 mL] cans of cola,
one 12 oz cup of tea, and three 1 oz [85 g] chocolate bars. Decaffeinated coffee,
tea, and cola are not considered to contain caffeine.)
15. Prior screen failure, randomization, participation, or enrollment in this study. If a
subject has successfully completed a study using LUM001 or SHP626, they may
participate in this study providing at least 30 days has passed since their last dose
of these investigational products and they have successfully completed all screening
16. Current use of any medication (including over-the-counter, herbal, or homeopathic
preparations) with the exception of those medications listed in Section 5.2.1.
(Current use is defined as use within 14 days of the first dose of investigational
17. An inability to follow a standardized diet and meal schedule or inability to fast, as
required during the study.
18. Colonoscopy, barium enema, or other tests that require a bowel cleansing within 4
weeks prior to the first dose of investigational product.
19. Subjects who report typically having less than 3 bowel movements per week or greater
than 3 bowel movements per day.
20. Use of antibiotics within 30 days prior to the first dose of investigational product.
21. Use of bile acid sequestrants within 30 days prior to the first dose of