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

Renal Failure Clinical Trial

— STRATO  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01438710
• Other study ID #: LCP-Tacro 3003
• Status: Completed
• Phase: Phase 3
• First received: September 20, 2011
• Last updated: September 15, 2015
• Start date: December 2011
• Est. completion date: July 2015

Study information

• Verified date: September 2015
• Source: Veloxis Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study will evaluate and measure symptomatic hand tremor in stable kidney transplant subjects on Prograf or generic tacrolimus maintenance therapy at baseline (pre-conversion) and following conversion to LCP-Tacro. This study will also evaluate the safety of LCP-Tacro compared with Prograf or generic tacrolimus

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: July 2015
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Renal Failure
• Tremor
• Tremors

Intervention

Drug:
• Prograf
Oral Prograf or generic tacrolimus doses will be taken b,i,d, consistently in 2 divided doses, once in the morning and once in the evening, to maintain trough level in the range of 3 to 12 ng/mL. Target trough level for the subject will be determined per clinical practice.
• LCP-Tacro
LCP-Tacro will be administered orally q.d. in the morning based on a conversion factor from Prograf or generic tacrolimus to LCP-Tacro of 0.7 for non-African American subjects and 0.85 for African American subjects to maintain target trough level of 3 to 12 ng/mL.

Locations

Country	Name	City	State
United States	Clinical Investigative Site 007	Aurora	Colorado
United States	Clinical Investigative Site 012	Dallas	Texas
United States	Clinical Investigative Site 004	Lexington	Kentucky
United States	Clinical Investigative Site 006	Los Angeles	California
United States	Clinical Investigative Site 008	Minneapolis	Minnesota
United States	Clinical Investigative Site 009	Nashiville	Tennessee
United States	Clinical Investigative Site 005	New Haven	Connecticut
United States	Clinical Investigative Site 002	Oklahoma City	Oklahoma
United States	Clinical Investigative Site 1049	San Diego	California
United States	Clinical Investigative Site 003	St Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Veloxis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluation of Hand Tremor and Stable Kidney Transplant Patients When Switched From Prograf to LCP-Tacro.	The primary efficacy endpoint is the mean change from baseline (ie Day 7) in the Fahn-Tolosa-Marin Clinical Rating Scale (FTM) for overall tremor score 7 days after (ie, Day 14) LCP-Tacro conversion.; The overall FTM score was 0 to 100 where higher scores denoted worst/more severe tremor.; Below the mean total score and standard deviation for each treatment is given in addition to the mean change.	14 days	No