A Study to Evaluate the Ability of Lupron Depot to Enhance Immune Function Following Bone Marrow Transplantation

• Sponsor: Abbott (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00275262
• Collaborator: Norwood Immunology Limited (Other), M.D. Anderson Cancer Center (Other), Dana-Farber Cancer Institute (Other)
• Enrollment: 25
• Locations: 4
• Arms: 2
• Patients Per Site: 6.3

Study Details

Study Description

Brief Summary

Phase 2 study, conducted in patients with Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, or mantle cell lymphoma undergoing high-dose chemotherapy and autologous stem cell transplantation.

Condition or Disease	Intervention/Treatment	Phase
Hodgkin Disease; Lymphoma, Non-Hodgkin; Multiple Myeloma; Mantle Cell Lymphoma	Drug: Leuprolide acetate depot (LAD) 11.25 mg 3 Month; Drug: Matched placebo	Phase 2

Detailed Description

This Phase 2 study will be conducted in patients with Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, or mantle cell lymphoma undergoing high-dose chemotherapy and autologous stem cell transplantation. Patients will be randomized to receive either LAD 11.25 mg 3 Month treatment or placebo and all patients will be vaccinated with KLH 6 months posttransplant. Patients will be evaluated to determine if the rate of immunologic recovery in the LAD group is enhanced compared with the placebo group.

Study Design

• Study Type: Interventional
• Actual Enrollment: 25 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Leuprolide Acetate to Enhance Immune Function Post-Autologous Stem Cell Transplantation
• Study Start Date: Feb 1, 2006
• Actual Primary Completion Date: Feb 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LAD 11.25 mg 3 Month Depot Three intramuscular injections LAD 11.25 mg 3 Month treatment administered approximately 3 months apart.	Drug: Leuprolide acetate depot (LAD) 11.25 mg 3 Month; LAD intramuscular injection 11.25 mg, 3 month duration. To stimulate immune response, a subcutaneous key limpet hemocyanin (KLH) vaccination injection (1 mg) was administered at Month 6.; Other Names: Lupron
Placebo Comparator: Placebo Comparator Three intramuscular injections of matched placebo administered approximately 3 months apart.	Drug: Matched placebo; Matched placebo intramuscular injection, 3 month duration. To stimulate immune response, a subcutaneous key limpet hemocyanin (KLH) vaccination injection (1 mg) was administered at Month 6.

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline in IgM Response (Mcg/mL) Before Keyhole Limpet Hemocyanin (KLH) Vaccination at Month 6 and After KLH Vaccination at Month 7 in Patients Who Received LAD or Placebo [Month 6 prevaccination (baseline) and Month 7 postvaccination]

   Patients received a subcutaneous injection of KLH vaccine 1 month after subjects received the third injection of LAD or placebo. Serum immunoglobulin IgM antibodies were determined by enzyme-linked immunosorbent assay (ELISA). Baseline is defined as the IgM concentration before the KLH vaccination. Change from baseline was calculated as the IgM value postvaccination minus the IgM value at prevaccination.

2. Mean Change From Baseline in IgG1 Response (Mcg/mL) Before KLH Vaccination at Month 6 and After KLH Vaccination at Month 7 in Patients Who Received LAD or Placebo [Month 6 prevaccination (baseline) and Month 7 postvaccination]

   Patients received a subcutaneous injection of KLH vaccine 1 month after subjects received the third injection of LAD or placebo. Serum immunoglobulin IgG1 antibodies were determined by enzyme-linked immunosorbent assay (ELISA). Baseline is defined as the IgG1 concentration before the KLH vaccination. Change from baseline was calculated as the IgG1 value postvaccination minus the IgG1 value at baseline.

3. Mean Change From Baseline in Interferon Gamma Response (Spots/1 Million Cells) Before KLH Vaccination at Month 6 and After KLH Vaccination at Month 7 in Patients Who Received LAD or Placebo [Month 6 prevaccination (baseline) and Month 7 postvaccination]

   Patients received a subcutaneous injection of KLH vaccine 1 month after subjects received the third injection of LAD or placebo. Interferon gamma was determined by enzyme-linked immunosorbent spot-forming cell (ELISpot). Baseline is defined as the interferon gamma concentration obtained before the KLH vaccination. Change from baseline was calculated as the interferon gamma value postvaccination minus the interferon gamma value at baseline.

Secondary Outcome Measures

1. Mean Change From Baseline in T Cell Excision Circles (TREC) Per 100,000 CD4+ Cells to Final Visit in Patients Treated With LAD (11.25 mg) or Placebo After Transplant [Pretransplant and posttransplant (Month 12)]

   CD4+ cells are a type of T cell. T cells are produced in the thymus and thymic function can be determined by TREC. By counting the number of TRECs present (only 1 copy per cell) within a population of CD4 cells, an assessment of T cell recovery and immune response is obtained. Mayo Medical Clinic. http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/87959. Accessed 17 MARCH 2010 The change from baseline is defined as posttransplant TREC/100,000 CD4+ cells minus pretransplant TREC /100,000 CD4+ cells.

2. Mean Change From Baseline in TREC Per 100,000 CD8+ Cells to Final Visit in Patients Treated With LAD (11.25 mg) or Placebo After Transplant [Pretransplant and posttransplant (Month 12)]

   CD8+ cells are a type of T cell. T cells are produced in the thymus and thymic function can be determined by TREC. By counting the number of TRECs present (only 1 copy per cell) within a population of CD8+ cells, an assessment of T cell recovery and immune response is obtained. Mayo Medical Clinic. http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/87959. Accessed 17 MARCH 2010 The change from baseline is defined as posttransplant TREC/100,000 CD8+ cells minus pretransplant TREC /100,000 CD8+ cells.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Must be female between the ages of 18 - 50 or if female > 50 years old have an estradiol concentration level >= 30 pg/mL and follicle stimulating hormone level < 40 mIU/mL, or male between the ages of 18-65 (inclusive).

2. Must have Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, or mantle cell lymphoma and be considered an appropriate candidate for hematopoietic stem cell transplant.

3. Multiple myeloma patients should have had a partial or complete response to chemotherapy.

4. Patients with Hodgkin's disease or non-Hodgkin's lymphoma who achieve a partial response to initial chemotherapy or first or second chemosensitive relapse, achieving a complete or partial response to salvage treatment. Patients in first remission with mantle cell lymphoma, or with intermediate or high grade lymphoma, presenting with high intermediate or high IPI (International Prognostic Index) scores are also eligible.

5. Must be seronegative for hepatitis C and HIV.

6. Must have received prior tetanus immunization

7. Must not have received prior KLH immunization.

8. Must have an ECOG performance status (PS) <= 1 or Karnofsky PS >= 70%.

9. Must have creatinine <= 2.0 mg/dL; ejection fraction > 45%; carbon monoxide diffusion in the lungs (DLCO) > 50% of predicted; serum bilirubin < 1.5 times the upper limit of normal unless Gilbert's syndrome, SGPT < 3 times normal value.

10. Must be more than 3 weeks from any prior surgery (except for central line placement) and have fully recovered from the effects of surgery.

11. Must have an absolute neutrophil count (ANC) >= 1,500 µL, platelet count >= 100,000/µL and hemoglobin >= 8.0 gm/dL within 21 days prior to randomization.

12. Must be able to return to the clinical site for follow-up visits.

13. Must be able to provide written consent.

Exclusion Criteria:

1. Must not have an uncontrolled life-threatening infection (or active infectious process requiring intravenous [IV] systemic medical therapy within 1 week prior to study enrollment).

2. Must not have a diagnosed or suspected schistosomiasis infection.

3. Must not have previously received hematopoietic stem cell transplantation.

4. Must not require a tandem transplant.

5. Must not be female with a positive pregnancy test, pregnant, or lactating and breast feeding, or wish to become pregnant during the course of the study. Must agree to use barrier method of contraception.

6. Must not be receiving estrogen or testosterone replacement therapy,phytoestrogen, phyto-testosterone, or oral contraceptives (patients may enroll if oral contraceptives are ceased prior to study entry), or have been administered Depo Provera within 3 months of entering the study.

7. Must not have had prior mediastinal or sternal radiation.

8. Must not have received any investigational drug other than antibiotics within 3 weeks prior to study drug administration or are scheduled to receive an investigational drug during the course of this study.

9. Must not have unstable cardiac arrhythmias, uncontrolled congestive heart failure, history of myocardial infarction (MI) or ischemia, stroke, or embolic events within 6 months before study start.

10. Must not have medical or psychiatric conditions that, in the opinion of the investigator, would compromise the patient's ability to participate in the study.

11. Must not be receiving or plan to receive palifermin (KGF).

12. Must not have a allergy to shellfish.

13. Must not have previously taken a GnRH analog within 18 months.

14. Must not be a woman who has undergone bilateral oophorectomy, or man with orchiectomy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Saint Louis	Missouri	United States	63110
2		New York	New York	United States	10021
3		Durham	North Carolina	United States	27710
4		Houston	Texas	United States	77030

Sponsors and Collaborators

• Abbott
• Norwood Immunology Limited
• M.D. Anderson Cancer Center
• Dana-Farber Cancer Institute

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00275262
• Other Study ID Numbers: L-BT04-093
• First Posted: Jan 11, 2006
• Last Update Posted: May 6, 2010
• Last Verified: Apr 1, 2010

• Keywords provided by , ,: Bone marrow transplantation; Hematopoietic stem cell transplantation; Hodgkin's disease; non-Hodgkin's lymphoma; multiple myeloma
• Additional relevant MeSH terms: Lymphoma; Multiple Myeloma; Lymphoma, Mantle-Cell; Hodgkin Disease; Lymphoma, Non-Hodgkin; Leuprolide

Study Results

Participant Flow

Arm/Group Title	Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month	Placebo
Arm/Group Description	Patients received 1 injection of LAD 11.25 mg every 3 months for a total treatment period of 9 months.	Patients received 1 injection of placebo every 3 months for a total treatment period of 9 months.
Period Title: Overall Study
STARTED	12	13
COMPLETED	6	4
NOT COMPLETED	6	9

Baseline Characteristics

Arm/Group Title	Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month	Placebo	Total
Arm/Group Description	Patients received 1 injection of LAD 11.25 mg every 3 months for a total treatment period of 9 months.	Patients received 1 injection of placebo every 3 months for a total treatment period of 9 months.	Total of all reporting groups
Overall Participants	12	13	25
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	13 100%	25 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.0 (10.16)	47.4 (7.04)	48.2 (8.53)
Sex: Female, Male (Count of Participants)
Female	3 25%	3 23.1%	6 24%
Male	9 75%	10 76.9%	19 76%
Region of Enrollment (participants) [Number]
United States	12 100%	13 100%	25 100%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline in IgM Response (Mcg/mL) Before Keyhole Limpet Hemocyanin (KLH) Vaccination at Month 6 and After KLH Vaccination at Month 7 in Patients Who Received LAD or Placebo
Description	Patients received a subcutaneous injection of KLH vaccine 1 month after subjects received the third injection of LAD or placebo. Serum immunoglobulin IgM antibodies were determined by enzyme-linked immunosorbent assay (ELISA). Baseline is defined as the IgM concentration before the KLH vaccination. Change from baseline was calculated as the IgM value postvaccination minus the IgM value at prevaccination.
Time Frame	Month 6 prevaccination (baseline) and Month 7 postvaccination

Outcome Measure Data

Analysis Population Description

Eight subjects from the LAD-treated arm and 5 subjects from the placebo-treated arm were assessed for IgM. These subjects received 3 doses of LAD or placebo, KLH vaccination, and had a blood collection suitable for analysis for primary endpoint although not all subjects completed the entire study.

Arm/Group Title	Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month	Placebo
Arm/Group Description	Patients received 1 injection of LAD 11.25 mg every 3 months for a total treatment period of 9 months.	Patients received 1 injection of placebo every 3 months for a total treatment period of 9 months.
Measure Participants	8	5
Mean IgM at baseline (mcg/mL)	4.0 (3.8)	3.0 (2.8)
Mean IgM change from baseline (mcg/mL)	2.91 (2.07)	0.57 (0.83)

2. Secondary Outcome

Title	Mean Change From Baseline in T Cell Excision Circles (TREC) Per 100,000 CD4+ Cells to Final Visit in Patients Treated With LAD (11.25 mg) or Placebo After Transplant
Description	CD4+ cells are a type of T cell. T cells are produced in the thymus and thymic function can be determined by TREC. By counting the number of TRECs present (only 1 copy per cell) within a population of CD4 cells, an assessment of T cell recovery and immune response is obtained. Mayo Medical Clinic. http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/87959. Accessed 17 MARCH 2010 The change from baseline is defined as posttransplant TREC/100,000 CD4+ cells minus pretransplant TREC /100,000 CD4+ cells.
Time Frame	Pretransplant and posttransplant (Month 12)

Outcome Measure Data

Analysis Population Description

Nine subjects from the LAD-treated arm and 7 subjects from the placebo-treated arm were assessed for TREC per 100,000 CD4+ cells. These subjects received 3 doses of LAD or placebo, KLH vaccination, and had a blood collection suitable for analysis for primary endpoint although not all subjects completed the entire study.

Arm/Group Title	Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month	Placebo
Arm/Group Description	Patients received 1 injection of LAD 11.25 mg every 3 months for a total treatment period of 9 months.	Patients received 1 injection of placebo every 3 months for a total treatment period of 9 months.
Measure Participants	9	7
Baseline TREC per 100,000 CD4+ cells	67.524 (47.0863)	173.712 (206.1733)
Mean change in TREC from baseline to final visit	522.321 (920.790)	-63.950 (235.561)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month, Placebo
	Comments	The final on treatment values were included in the analysis.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.125
	Comments
	Method	ANOVA
	Comments	The statistical method used for a 1-way ANOVA between treatment groups.

3. Secondary Outcome

Title	Mean Change From Baseline in TREC Per 100,000 CD8+ Cells to Final Visit in Patients Treated With LAD (11.25 mg) or Placebo After Transplant
Description	CD8+ cells are a type of T cell. T cells are produced in the thymus and thymic function can be determined by TREC. By counting the number of TRECs present (only 1 copy per cell) within a population of CD8+ cells, an assessment of T cell recovery and immune response is obtained. Mayo Medical Clinic. http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/87959. Accessed 17 MARCH 2010 The change from baseline is defined as posttransplant TREC/100,000 CD8+ cells minus pretransplant TREC /100,000 CD8+ cells.
Time Frame	Pretransplant and posttransplant (Month 12)

Outcome Measure Data

Analysis Population Description

Eight subjects from the LAD-treated arm and 5 subjects from the placebo-treated arm were assessed for TREC per 100,000 CD8+ cells. These subjects received 3 doses of LAD or placebo, KLH vaccination, and had a blood collection suitable for analysis for primary endpoint although not all subjects completed the entire study.

Arm/Group Title	Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month	Placebo
Arm/Group Description	Patients received 1 injection of LAD 11.25 mg every 3 months for a total treatment period of 9 months.	Patients received 1 injection of placebo every 3 months for a total treatment period of 9 months.
Measure Participants	9	7
Baseline mean for TREC per 100,000 CD8+ cells	181.673 (209.7599)	364.414 (280.3465)
Mean change in TREC from baseline to final visit	-10.811 (343.061)	-184.084 (282.405)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month, Placebo
	Comments	The final on treatment values were included in the analysis.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.299
	Comments
	Method	ANOVA
	Comments	The statistical method used for a 1-way ANOVA between treatment groups.

4. Primary Outcome

Title	Mean Change From Baseline in IgG1 Response (Mcg/mL) Before KLH Vaccination at Month 6 and After KLH Vaccination at Month 7 in Patients Who Received LAD or Placebo
Description	Patients received a subcutaneous injection of KLH vaccine 1 month after subjects received the third injection of LAD or placebo. Serum immunoglobulin IgG1 antibodies were determined by enzyme-linked immunosorbent assay (ELISA). Baseline is defined as the IgG1 concentration before the KLH vaccination. Change from baseline was calculated as the IgG1 value postvaccination minus the IgG1 value at baseline.
Time Frame	Month 6 prevaccination (baseline) and Month 7 postvaccination

Outcome Measure Data

Analysis Population Description

Eight subjects from the LAD-treated arm and 5 subjects from the placebo-treated arm were assessed for IgG1. These subjects received 3 doses of LAD or placebo, KLH vaccination, and had a blood collection suitable for analysis for primary endpoint although not all subjects completed the entire study.

Arm/Group Title	Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month	Placebo
Arm/Group Description	Patients received 1 injection of LAD 11.25 mg every 3 months for a total treatment period of 9 months.	Patients received 1 injection of placebo every 3 months for a total treatment period of 9 months.
Measure Participants	8	5
Mean IgG1 at baseline (mcg/mL)	8.6 (9.1)	10.8 (11.6)
Mean IgG1 change from baseline (mcg/mL)	46.16 (44.01)	16.76 (28.15)

5. Primary Outcome

Title	Mean Change From Baseline in Interferon Gamma Response (Spots/1 Million Cells) Before KLH Vaccination at Month 6 and After KLH Vaccination at Month 7 in Patients Who Received LAD or Placebo
Description	Patients received a subcutaneous injection of KLH vaccine 1 month after subjects received the third injection of LAD or placebo. Interferon gamma was determined by enzyme-linked immunosorbent spot-forming cell (ELISpot). Baseline is defined as the interferon gamma concentration obtained before the KLH vaccination. Change from baseline was calculated as the interferon gamma value postvaccination minus the interferon gamma value at baseline.
Time Frame	Month 6 prevaccination (baseline) and Month 7 postvaccination

Outcome Measure Data

Analysis Population Description

Six subjects from the LAD-treated arm and 5 subjects from the placebo-treated arm were assessed for interferon gamma. These subjects received 3 doses of LAD or placebo, KLH vaccination, and had a blood collection suitable for analysis for primary endpoint although not all subjects completed the entire study.

Arm/Group Title	Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month	Placebo
Arm/Group Description	Patients received 1 injection of LAD 11.25 mg every 3 months for a total treatment period of 9 months.	Patients received 1 injection of placebo every 3 months for a total treatment period of 9 months.
Measure Participants	6	5
Mean interferon gamma at baseline	0.2 (3.2)	-1.4 (3.2)
Mean interferon gamma change from baseline	2.09 (4.85)	10.25 (11.41)

Adverse Events

Arm/Group Title	Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month		Placebo
Arm/Group Description	Patients received 1 injection of LAD 11.25 mg every 3 months for a total treatment period of 9 months.		Patients received 1 injection of placebo every 3 months for a total treatment period of 9 months.
All Cause Mortality
	Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/12 (50%)		4/13 (30.8%)
Blood and lymphatic system disorders
Febrile neutropenia	1/12 (8.3%)		1/13 (7.7%)
Thrombocytopenia	0/12 (0%)		1/13 (7.7%)
General disorders
Pyrexia	1/12 (8.3%)		0/13 (0%)
Infections and infestations
Gastroenteritis	1/12 (8.3%)		0/13 (0%)
Pneumonia	0/12 (0%)		1/13 (7.7%)
Pneumonia mycoplasmal	1/12 (8.3%)		0/13 (0%)
Respiratory tract infection bacterial	1/12 (8.3%)		0/13 (0%)
Respiratory tract infection viral	0/12 (0%)		1/13 (7.7%)
Staphylococcal bacteremia	0/12 (0%)		1/13 (7.7%)
Metabolism and nutrition disorders
Failure to thrive	0/12 (0%)		1/13 (7.7%)
Hypokalemia	0/12 (0%)		1/13 (7.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Multiple myeloma	0/12 (0%)		1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/12 (8.3%)		0/13 (0%)
Vascular disorders
Deep vein thrombosis	1/12 (8.3%)		0/13 (0%)
Other (Not Including Serious) Adverse Events
	Leuprolide Acetate Depot (LAD) 11.25 mg 3 Month		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/12 (58.3%)		7/13 (53.8%)
Blood and lymphatic system disorders
Lymphopenia	0/12 (0%)		1/13 (7.7%)
Neutropenia	0/12 (0%)		1/13 (7.7%)
Cardiac disorders
Palpitations	1/12 (8.3%)		0/13 (0%)
Endocrine disorders
Hypogonadism	1/12 (8.3%)		0/13 (0%)
Gastrointestinal disorders
Constipation	0/12 (0%)		1/13 (7.7%)
Diarrhea	0/12 (0%)		1/13 (7.7%)
Food poisoning	1/12 (8.3%)		0/13 (0%)
Gastroesophageal reflux disease	0/12 (0%)		1/13 (7.7%)
General disorders
Axillary pain	0/12 (0%)		1/13 (7.7%)
Fatigue	0/12 (0%)		1/13 (7.7%)
Injection site swelling	1/12 (8.3%)		0/13 (0%)
Mucosal inflammation	0/12 (0%)		1/13 (7.7%)
Edema peripheral	0/12 (0%)		1/13 (7.7%)
Pyrexia	0/12 (0%)		2/13 (15.4%)
Infections and infestations
Bronchitis	0/12 (0%)		1/13 (7.7%)
Central line infection	0/12 (0%)		1/13 (7.7%)
Herpes zoster	1/12 (8.3%)		0/13 (0%)
Respiratory tract infection	0/12 (0%)		1/13 (7.7%)
Upper respiratory tract infection	0/12 (0%)		1/13 (7.7%)
Urinary tract infection	1/12 (8.3%)		0/13 (0%)
Investigations
Alanine aminotransferase increased	0/12 (0%)		1/13 (7.7%)
Blood alkaline phosphatase increased	0/12 (0%)		1/13 (7.7%)
Blood creatinine increased	1/12 (8.3%)		1/13 (7.7%)
Hemoglobin decreased	0/12 (0%)		1/13 (7.7%)
Metabolism and nutrition disorders
Hyperkalemia	0/12 (0%)		1/13 (7.7%)
Hypoalbuminemia	0/12 (0%)		1/13 (7.7%)
Hypocalcemia	0/12 (0%)		1/13 (7.7%)
Hypomagnesemia	1/12 (8.3%)		0/13 (0%)
Hyponatremia	0/12 (0%)		1/13 (7.7%)
Musculoskeletal and connective tissue disorders
Back pain	0/12 (0%)		2/13 (15.4%)
Neck pain	0/12 (0%)		1/13 (7.7%)
Osteoporosis	1/12 (8.3%)		0/13 (0%)
Nervous system disorders
Dizziness	1/12 (8.3%)		0/13 (0%)
Headache	1/12 (8.3%)		0/13 (0%)
Psychiatric disorders
Anxiety	0/12 (0%)		1/13 (7.7%)
Insomnia	0/12 (0%)		1/13 (7.7%)
Mental status changes	0/12 (0%)		1/13 (7.7%)
Reproductive system and breast disorders
Erectile dysfunction	0/12 (0%)		1/13 (7.7%)
Respiratory, thoracic and mediastinal disorders
Cough	1/12 (8.3%)		0/13 (0%)
Dyspnea	0/12 (0%)		2/13 (15.4%)
Rhinitis allergic	1/12 (8.3%)		1/13 (7.7%)
Rhinorrhea	0/12 (0%)		1/13 (7.7%)
Sleep apnea syndrome	0/12 (0%)		1/13 (7.7%)
Skin and subcutaneous tissue disorders
Psoriasis	1/12 (8.3%)		0/13 (0%)
Rash	0/12 (0%)		1/13 (7.7%)
Vascular disorders
Hypertension	0/12 (0%)		1/13 (7.7%)

Limitations/Caveats

The study was terminated early because of slow enrollment. For the primary endpoint, changes from baseline within each treatment group were analyzed. Between treatment group comparisons were not performed because the sample size was too small.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Abbott requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. Abbott requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if Abbott needs to secure patent or proprietary protection.