Switching Study of Kidney Transplant Patients With Tremor to LCP-Tacro (STRATO)

This is a 2 sequence, open-label, multicenter, prospective Phase 3b clinical study to access
drug-induced hand tremors in stable kidney transplant subjects converted from Prograf
(tacro-limus, Astellas Pharma US, Inc., Deerfield, IL) or generic tacrolimus twice daily
(b.i.d.) to LCP-Tacro tablets (tacrolimus, Veloxis Pharmaceuticals A/S, Horsholm, Denmark)
once daily (q.d.). The trial is designed to determine if the test drug LCP-Tacro, is
associated with fewer and/or less severe drug-induced hand tremor than observed with Prograf
or generic tacrolimus treatment; each therapy is to be concomitantly administered with
mycophenolate mofetil (MMF), mycophenolate sodium (MPS), including generic versions of each,
and/or prednisone or equivalent as long as doses remain stable during the study. All
prophylaxis and other medication will be allowed per standard of care (SOC) in each of the
participating sites; no medication that interacts with the pharmacokinetics (PK) of
tacrolimus is allowed unless subjects who are recipients of a renal transplant at least 1
month and not more than 5 years prior to enrollment. Following screening, study visits will
be conducted over a 2-week treatment period with consists of 1 week of Prograf or generic
tacrolimus SOC, and 1 week of LCP-Tacro. Subjects who qualify for extended use of LCP-Tacro
can continue LCP-Tacro treatment for additional 2 years. This decision will be made at the
discretion of the physician and subject.

Inclusion Criteria:

1. Subjects must be able to give written consent

2. Men and women between 18 and 65 years of age who are recipients of a kidney
transplant between 1 month and 5 years prior to the screening date

3. Subjects with at least one complaint of tremor and existence of postural tremor or
action tremor on finger to nose as demonstrated by a score of at least 2 of any of
the 4 upper extremity (UE) postural or action and intention assessments on the FTM
clinical rating scale

4. Subjects experiencing symptomatic drug-induced hand tremor associated with use of
Prograf or generic tacrolimus as demonstrated by responding "no" to each of the
following question: "Did you have a tremor that you noticed prior to starting Prograf
or generic tacrolimus for your kidney transplant?", or "Are you aware of a tremor
that runs in your family?"

5. Subjects taking a stable dose of oral Prograf or generic tacrolimus capsules for at
least 7 days with trough levels of tacrolimus between 3 to 12 ng/mL. Subjects must
maintain tacrolimus trough levels in this range during the 7 day Prograf or generic
tacrolimus treatment phase (note that 1 dose adjustment at Study Day 3 [a.m.dose] is
allowed for those subjects whose Day0/1 trough level is out of range.

6. Women of childbearing potential must have a negative serum pregnancy test within 7
days before study start.

Exclusion Criteria:

1. Recipients of any transplants including organ other than kidney and bone marrow

2. Subjects with an estimated glomerular filtration rate (eGFR) (MDRD7) <30mL/min at
Screening

3. Subjects incapable of understanding the purposed and risks of the study, who cannot
give written informed consent and who are unwilling or unable to comply with study
protocol requirements

4. Pregnant or nursing women

5. Subjects with reproductive potential who are unwilling/unable to use a double barrier
method of contraception

6. Subjects who were treated with any other investigational agent within 3 months prior
to screening

7. Subjects who are taking drugs that are likely to affect the PK levels of tacrolimus
and are not on a stable dose of those medications (see Appendix 1)

8. Subjects who have essential tremor, Parkinsonism, or tremor from any cause other than
tacrolimus-induced tremor;

9. Subjects who are taking or had been taking any drug within the past 30 days that is
well known to promote tremors, including: amiodarone, beta-agonist inhalers (such as
albuterol), cyclosporine, lithium, metoclopramide, theophylline, or valproate,or
taking within the past 6 months the dopamine blocking agents (antipsychotics) (note,
other such medication may be considered on a case-by-case basis at the discretion of
the investigator);

10. Subjects who taking drugs that reduce tremor, and are not on stable doses of the
treatment (ie, had not been taking the medication for a minimum of 30 days),
including: gabapentin (note, other such medications may be considered on a
case-by-case basis at the discretion of the investigator);

11. Subjects on concurrent immunosuppression with MMD (CellCept) of MPS delayed-release
tables (Myfortic), or generic versions of these medication, who have not been on
stable doses at least 7 days prior to screening

12. Subjects receiving prednisone or equivalent at a dose >10 mg per day

13. Either subjects with an episode of acute rejection requiring treatment or subjects
with an episode of biopsy-proven or suspected acute rejections that requires
treatment within 3 months of screening

14. Subjects who are being actively treated for cancer (with the exception of
non-invasive basal cell or squamous cell) or human immunodeficiency virus (HIV)

15. Subjects with any form of current drug or alcohol abuse