Steroid Treatment for Hypereosinophilic Syndrome

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT01524536
• Collaborator: (none)
• Enrollment: 26
• Location: 1
• Arm: 1
• Actual Duration (Months): 105.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

Background:

• Hypereosinophilic syndrome (HES) is a disorder in which the body has too many eosinophils (a type of white blood cell). Too many eosinophils in HES can cause damage to the heart, nerves, or skin. Certain drugs can help lower eosinophil counts to prevent tissue damage. Corticosteroids, such as prednisone, are used for initial therapy in this disorder. Although most people respond to prednisone, some people develop side effects from it, or do not respond very well to treatment. Better ways of determining the dose to give could help to decide on the best therapy for HES.

Objectives:

• To determine whether a single-dose of prednisone can be used to predict which people with hypereosinophilia respond to treatment.

• To study lack of response to steroid treatment in people with HES.

Eligibility:

Inclusion criteria:

• Individuals with hypereosinophilic syndrome with high eosinophil counts.

• Individuals who are willing to have blood drawn before and after getting steroids.

Exclusion criteria:

• Individuals who are on more than 10mg of prednisone (or similar drug)

• Individuals with hypereosinophilic syndrome who are on other medications that could interfere with the study

• Women who are pregnant or breast-feeding

• Individuals who have a known gene mutation associated with chronic eosinophilic leukemia

• Children less than 18 years old who weigh less than 48kg or 106lb

Design:

• Participants will have a screening visit with a physical exam and medical history. Blood and urine samples will be collected.

• Participants will have a single dose of the steroid prednisone by mouth in the morning. Blood samples will be collected 2, 4, 24 hours after this dose.

• On the day after the steroid dose, participants will provide another blood sample in the morning.

• Participants will start to take prednisone daily when they return home. Blood samples will be collected weekly at the participant s doctor s office. The dose of prednisone will be lowered depending on the weekly eosinophil count. We will try to get each person on the lowest dose of prednisone possible that will control the disorder. Participants who do not respond or have severe side effects will be taken off prednisone. Other treatments will be considered for people who do not respond to steroids. The goal is to evaluate the response to prednisone. Our research will try to figure out why some people do not respond to steroids. Most people will complete the study within 6 to 16 weeks, depending on their response to prednisone.

Condition or Disease	Intervention/Treatment	Phase
Eosinophilia; Hypereosinophilic Syndrome; Leukocyte Disorder; Hematologic Diseases	Drug: prednisone	Phase 4

Detailed Description

This study aims to develop a model to determine whether a single, oral, weight-based dose of glucocorticoid (GC) can predict clinical and biologic response to GC s over the long term in subjects with hypereosinophilic syndrome (HES). Subjects with FIP1L1/PDGFRalpha-negative HES, who are symptomatic with eosinophil count >1500/microL and receiving less than or equal to10 mg prednisone daily, will be enrolled. A single oral dose of prednisone (1 mg/kg rounded to the nearest 5mg) will be administered. Eosinophil count and various laboratory parameters will be assessed at 2 hours, 4 hours and 24 hours following prednisone administration (investigators will be blinded to the results of the eosinophil counts). The subjects will then begin GC therapy at 30 mg prednisone daily followed by a standardized taper. The lowest dose of GC at which symptoms and eosinophilia are controlled will be compared to the change in eosinophil count at 2, 4 and 24 hours post-challenge. Mechanisms and in vitro correlates of GC resistance will also be explored.

Study Design

• Study Type: Interventional
• Actual Enrollment: 26 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Assessment of Glucocorticoid Responsiveness and Mechanisms of Resistance in Hypereosinophilic Syndromes
• Actual Study Start Date: Feb 16, 2012
• Actual Primary Completion Date: Dec 10, 2020
• Actual Study Completion Date: Dec 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Other: Steroid Challenge A single oral dose of prednisone (1 mg/kg rounded to the nearest 5mg) was administered to all participants. The following day, participant began glucocorticoid therapy of prednisone 30 mg oral daily for one week followed by a standardized taper until a minimally effective dose was achieved or participant tapered to prednisone 5 mg oral daily.	Drug: prednisone; Glucocorticoids (GC) are considered the first- line therapy for hypereosinophilic syndrome.

Outcome Measures

Primary Outcome Measures

1. Mean Percent Change in Eosinophil Count After Glucocorticoid Challenge [24 hours]

   Response to glucocorticoid challenge as assessed by the percentage of the eosinophil count 24 hours post-glucocorticoid challenge relative to the Baseline AEC for each participant. Measure Description (%): Percent of baseline AEC is defined as the Absolute Eosinophil Count at 24 hours divided by the Absolute Eosinophil Count at Baseline *100.

Secondary Outcome Measures

1. Participants With Glucocorticoid Responsiveness - IHES Variant [Baseline (Day 1)]

   Participants with idiopathic hypereosinophilic syndromes (IHES) that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.

2. Participants With Glucocorticoid Responsiveness - LHES Variant [Baseline (Day 1)]

   Participants with lymphoid hypereosinophilic syndromes (LHES) that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.

3. Participants With Glucocorticoid Responsiveness - MHES Variant [Baseline (Day 1)]

   Participants with myeloid hypereosinophilic syndromes (MHES) that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.

4. Participants With Glucocorticoid Responsiveness - Overlap HES Subtypes [Baseline (Day 1)]

   Participants with overlap hypereosinophilic syndromes that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.

5. Mean Baseline IgE Level [Baseline (Day 1)]

   Mean baseline immunoglobulin E (IgE) level in participants prior to initiation of glucocorticoid

6. Mean Baseline Absolute Eosinophil Count [Baseline (Day 1)]

   Mean baseline absolute eosinophil count in participants prior to initiation of glucocorticoids

7. Participants With Glucocorticoid Responsiveness - Cardiac Involvement [Baseline (Day 1)]

   Cardiac involvement in participants with hypereosinophilic syndromes (HES)

8. Participants With Glucocorticoid Responsiveness - Pulmonary Involvement [Baseline (Day 1)]

   Pulmonary involvement in participants with hypereosinophilic syndromes (HES)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

• SUBJECT INCLUSION CRITERIA:

Subjects on Protocol #94-I-0079 will be eligible for participation in the study only if all of the following criteria apply:

1. Subjects must be 7 years of age or older to enroll

2. Subject meets diagnostic criteria for HES (AEC >1500/microL, absence of a secondary cause and signs and/or symptoms attributable to the eosinophilia)

3. AEC greater than 1500 microL obtained within 14 days prior to enrollment

4. Willingness to perform the timed steroid challenge

5. Appropriate candidate for GC treatment after challenge

6. Willingness to have samples stored for future research

SUBJECT EXCLUSION CRITERIA:

A subject will not be eligible to participate in the study if any of the following apply:

1. Receiving >10 mg prednisone or equivalent at the time of enrollment.

2. Receiving less than or equal to 10 mg of prednisone or equivalent but have not been on a fixed dose for at least 3 weeks (subjects on a current corticosteroid taper will be excluded).

3. AEC less than or equal to 1500/microl on the day of the steroid challenge

4. Use of immunomodulatory medications, (other than less than or equal to 10 mg/day prednisone) including but not limited to biologics, within the past 6 months.

5. Pregnant at the time of screening.

6. Have a known mutation in the FIP1L1-PDGFR gene.

7. Any condition that, in the opinion of the investigator, places the subject at undue risk by participating in the protocol.

8. Weight less than 48 kg (106 lbs) in subjects less than 18 years of age.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Paneez Khoury, M.D., National Institute of Allergy and Infectious Diseases (NIAID)

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 4, 2020

More Information

Additional Information:

• NIH Clinical Center Detailed Web Page

Publications

• Hamilos DL, Leung DY, Muro S, Kahn AM, Hamilos SS, Thawley SE, Hamid QA. GRbeta expression in nasal polyp inflammatory cells and its relationship to the anti-inflammatory effects of intranasal fluticasone. J Allergy Clin Immunol. 2001 Jul;108(1):59-68.
• Ogbogu PU, Bochner BS, Butterfield JH, Gleich GJ, Huss-Marp J, Kahn JE, Leiferman KM, Nutman TB, Pfab F, Ring J, Rothenberg ME, Roufosse F, Sajous MH, Sheikh J, Simon D, Simon HU, Stein ML, Wardlaw A, Weller PF, Klion AD. Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy. J Allergy Clin Immunol. 2009 Dec;124(6):1319-25.e3. doi: 10.1016/j.jaci.2009.09.022.
• Prin L, Lefebvre P, Gruart V, Capron M, Storme L, Formstecher P, Loiseau S, Capron A. Heterogeneity of human eosinophil glucocorticoid receptor expression in hypereosinophilic patients: absence of detectable receptor correlates with resistance to corticotherapy. Clin Exp Immunol. 1989 Dec;78(3):383-9.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT01524536
• Other Study ID Numbers: 120026; 12-I-0026
• First Posted: Feb 2, 2012
• Last Update Posted: Feb 15, 2022
• Last Verified: Feb 22, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Hypereosinophilia; Hypereosinophilic Syndrome; Corticosteroids; Therapy; HES
• Additional relevant MeSH terms: Hematologic Diseases; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Syndrome; Prednisone

Study Results

Participant Flow

Pre-assignment Detail	26 participants were consented to protocol but three did not meet the eligibility criteria so did not start study.

Arm/Group Title	Steroid Challenge
Arm/Group Description	A single oral dose of prednisone (1 mg/kg rounded to the nearest 5mg) was administered to all participants. The following day, participant began glucocorticoid therapy of prednisone 30 mg oral daily for one week followed by a standardized taper until a minimally effective dose was achieved or participant tapered to prednisone 5 mg oral daily.
Period Title: Overall Study
STARTED	23
COMPLETED	23
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Steroid Challenge
Arm/Group Description	A single oral dose of prednisone (1 mg/kg rounded to the nearest 5mg) was administered to all participants. The following day, participant began glucocorticoid therapy of prednisone 30 mg oral daily for one week followed by a standardized taper until a minimally effective dose was achieved or participant tapered to prednisone 5 mg oral daily.
Overall Participants	23
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	22 95.7%
>=65 years	1 4.3%
Sex: Female, Male (Count of Participants)
Female	12 52.2%
Male	11 47.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 26.1%
Not Hispanic or Latino	17 73.9%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 8.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 4.3%
White	15 65.2%
More than one race	1 4.3%
Unknown or Not Reported	4 17.4%

Outcome Measures

1. Primary Outcome

Title	Mean Percent Change in Eosinophil Count After Glucocorticoid Challenge
Description	Response to glucocorticoid challenge as assessed by the percentage of the eosinophil count 24 hours post-glucocorticoid challenge relative to the Baseline AEC for each participant. Measure Description (%): Percent of baseline AEC is defined as the Absolute Eosinophil Count at 24 hours divided by the Absolute Eosinophil Count at Baseline *100.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

All participants who received the single challenge dose of prednisone

Arm/Group Title	Steroid Challenge - Responders	Steroid Challenge - Non-responders
Arm/Group Description	A single oral dose of prednisone (1 mg/kg rounded to the nearest 5mg) was administered to all participants. The following day, participant began glucocorticoid therapy of prednisone 30 mg oral daily for one week followed by a standardized taper until a minimally effective dose was achieved or participant tapered to prednisone 5 mg oral daily.	A single oral dose of prednisone (1 mg/kg rounded to the nearest 5mg) was administered to all participants. The following day, participant began glucocorticoid therapy of prednisone 30 mg oral daily for one week followed by a standardized taper until a minimally effective dose was achieved or participant tapered to prednisone 5 mg oral daily.
Measure Participants	16	7
Mean (95% Confidence Interval) [percentage of eosinophil count]	-69.6	-13.6

2. Secondary Outcome

Title	Participants With Glucocorticoid Responsiveness - IHES Variant
Description	Participants with idiopathic hypereosinophilic syndromes (IHES) that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Time Frame	Baseline (Day 1)

Outcome Measure Data

Analysis Population Description

All participants who received the prednisone challenge and completed dose course post challenge

Arm/Group Title	Steroid Challenge - Glucocorticoid Responsiveness	Steroid Challenge - Glucocorticoid Suboptimal Responsiveness	Steroid Challenge - Glucocorticoid Unresponsiveness
Arm/Group Description	Participants with hypereosinophilic syndromes (IHES) that achieved glucocorticoid responsiveness defined as final minimally effective dose of prednisone of 0mg-15mg	Participants with hypereosinophilic syndromes (HES) with suboptimal glucocorticoid responsiveness defined as achieving final minimally effective dose of prednisone of 16mg-40mg	Participants with hypereosinophilic syndromes (HES) that were not responsive to prednisone defined as no decline of absolute eosinophil count (AEC) below 1000/mm^3 after one week of prednisone 30 mg daily, followed by 2 days of prednisone 60 mg daily
Measure Participants	11	5	7
Count of Participants [Participants]	6 26.1%	2 NaN	2 NaN

3. Secondary Outcome

Title	Participants With Glucocorticoid Responsiveness - LHES Variant
Description	Participants with lymphoid hypereosinophilic syndromes (LHES) that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Time Frame	Baseline (Day 1)

Outcome Measure Data

Analysis Population Description

All participants who received the prednisone challenge and completed dose course post challenge

Arm/Group Title	Steroid Challenge - Glucocorticoid Responsiveness	Steroid Challenge - Glucocorticoid Suboptimal Responsiveness	Steroid Challenge - Glucocorticoid Unresponsiveness
Arm/Group Description	Participants with hypereosinophilic syndromes (HES) that achieved glucocorticoid responsiveness defined as final minimally effective dose of prednisone of 0mg-15mg	Participants with hypereosinophilic syndromes (HES) with suboptimal glucocorticoid responsiveness defined as achieving final minimally effective dose of prednisone of 16mg-40mg	Participants with hypereosinophilic syndromes (HES) that were not responsive to prednisone defined as no decline of absolute eosinophil count (AEC) below 1000/mm^3 after one week of prednisone 30 mg daily, followed by 2 days of prednisone 60 mg daily.
Measure Participants	11	5	7
Count of Participants [Participants]	2 8.7%	1 NaN	2 NaN

4. Secondary Outcome

Title	Participants With Glucocorticoid Responsiveness - MHES Variant
Description	Participants with myeloid hypereosinophilic syndromes (MHES) that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Time Frame	Baseline (Day 1)

Outcome Measure Data

Analysis Population Description

All participants who received the prednisone challenge and completed dose course post challenge

Arm/Group Title	Steroid Challenge - Glucocorticoid Responsiveness	Steroid Challenge - Glucocorticoid Suboptimal Responsiveness	Steroid Challenge - Glucocorticoid Unresponsiveness
Arm/Group Description	Participants with hypereosinophilic syndromes (HES) that achieved glucocorticoid responsiveness defined as final minimally effective dose of prednisone of 0mg-15mg	Participants with hypereosinophilic syndromes (HES) with suboptimal glucocorticoid responsiveness defined as achieving final minimally effective dose of prednisone of 16mg-40mg	Participants with hypereosinophilic syndromes (HES) that were not responsive to prednisone defined as no decline of absolute eosinophil count (AEC) below 1000/mm^3 after one week of prednisone 30 mg daily, followed by 2 days of prednisone 60 mg daily
Measure Participants	11	5	7
Count of Participants [Participants]	0 0%	0 NaN	1 NaN

5. Secondary Outcome

Title	Participants With Glucocorticoid Responsiveness - Overlap HES Subtypes
Description	Participants with overlap hypereosinophilic syndromes that achieved glucocorticoid responsiveness, suboptimal responsiveness, or without response.
Time Frame	Baseline (Day 1)

Outcome Measure Data

Analysis Population Description

All participants who received the prednisone challenge and completed dose course post challenge

Arm/Group Title	Steroid Challenge - Glucocorticoid Responsiveness	Steroid Challenge - Glucocorticoid Suboptimal Responsiveness	Steroid Challenge - Glucocorticoid Unresponsiveness
Arm/Group Description	Participants with hypereosinophilic syndromes (HES) that achieved glucocorticoid responsiveness defined as final minimally effective dose of prednisone of 0mg-15mg	Participants with hypereosinophilic syndromes (HES) with suboptimal glucocorticoid responsiveness defined as achieving final minimally effective dose of prednisone of 16mg-40mg	Participants with hypereosinophilic syndromes (HES) that were not responsive to prednisone defined as no decline of absolute eosinophil count (AEC) below 1000/mm^3 after one week of prednisone 30 mg daily, followed by 2 days of prednisone 60 mg daily
Measure Participants	11	5	7
Count of Participants [Participants]	3 13%	2 NaN	1 NaN

6. Secondary Outcome

Title	Mean Baseline IgE Level
Description	Mean baseline immunoglobulin E (IgE) level in participants prior to initiation of glucocorticoid
Time Frame	Baseline (Day 1)

Outcome Measure Data

Analysis Population Description

All participants who received the prednisone challenge and completed dose course post challenge

Arm/Group Title	Steroid Challenge - Glucocorticoid Responsiveness	Steroid Challenge - Glucocorticoid Suboptimal Responsiveness	Steroid Challenge - Glucocorticoid Unresponsiveness
Arm/Group Description	Participants with hypereosinophilic syndromes (HES) that achieved glucocorticoid responsiveness defined as final minimally effective dose of prednisone of 0mg-15mg	Participants with hypereosinophilic syndromes (HES) with suboptimal glucocorticoid responsiveness defined as achieving final minimally effective dose of prednisone of 16mg-40mg	Participants with hypereosinophilic syndromes (HES) that were not responsive to prednisone defined as no decline of absolute eosinophil count (AEC) below 1000/mm^3 after one week of prednisone 30 mg daily, followed by 2 days of prednisone 60 mg daily
Measure Participants	11	5	7
Geometric Mean (95% Confidence Interval) [IU/mL]	285.2	1171.5	434.8

7. Secondary Outcome

Title	Mean Baseline Absolute Eosinophil Count
Description	Mean baseline absolute eosinophil count in participants prior to initiation of glucocorticoids
Time Frame	Baseline (Day 1)

Outcome Measure Data

Analysis Population Description

All participants who received the prednisone challenge and completed dose course post challenge

Arm/Group Title	Steroid Challenge - Glucocorticoid Responsiveness	Steroid Challenge - Glucocorticoid Suboptimal Responsiveness	Steroid Challenge - Glucocorticoid Unresponsiveness
Arm/Group Description	Participants with hypereosinophilic syndromes (HES) that achieved glucocorticoid responsiveness defined as final minimally effective dose of prednisone of 0mg-15mg	Participants with hypereosinophilic syndromes (HES) with suboptimal glucocorticoid responsiveness defined as achieving final minimally effective dose of prednisone of 16mg-40mg	Participants with hypereosinophilic syndromes (HES) that were not responsive to prednisone defined as no decline of absolute eosinophil count (AEC) below 1000/mm^3 after one week of prednisone 30 mg daily, followed by 2 days of prednisone 60 mg daily
Measure Participants	11	5	7
Geometric Mean (95% Confidence Interval) [10^3 cells per microliter]	2.81	3.85	5.90

8. Secondary Outcome

Title	Participants With Glucocorticoid Responsiveness - Cardiac Involvement
Description	Cardiac involvement in participants with hypereosinophilic syndromes (HES)
Time Frame	Baseline (Day 1)

Outcome Measure Data

Analysis Population Description

All participants who received the prednisone challenge and completed dose course post challenge

Arm/Group Title	Steroid Challenge - Glucocorticoid Responsiveness	Steroid Challenge - Glucocorticoid Suboptimal Responsiveness	Steroid Challenge - Glucocorticoid Unresponsiveness
Arm/Group Description	Participants with hypereosinophilic syndromes (HES) that achieved glucocorticoid responsiveness defined as final minimally effective dose of prednisone of 0mg-15mg	Participants with hypereosinophilic syndromes (HES) with suboptimal glucocorticoid responsiveness defined as achieving final minimally effective dose of prednisone of 16mg-40mg	Participants with hypereosinophilic syndromes (HES) that were not responsive to prednisone defined as no decline of absolute eosinophil count (AEC) below 1000/mm^3 after one week of prednisone 30 mg daily, followed by 2 days of prednisone 60 mg daily
Measure Participants	11	5	7
Count of Participants [Participants]	1 4.3%	0 NaN	4 NaN

9. Secondary Outcome

Title	Participants With Glucocorticoid Responsiveness - Pulmonary Involvement
Description	Pulmonary involvement in participants with hypereosinophilic syndromes (HES)
Time Frame	Baseline (Day 1)

Outcome Measure Data

Analysis Population Description

All participants who received the prednisone challenge and completed dose course post challenge

Arm/Group Title	Steroid Challenge - Glucocorticoid Responsiveness	Steroid Challenge - Glucocorticoid Suboptimal Responsiveness	Steroid Challenge - Glucocorticoid Unresponsiveness
Arm/Group Description	Participants with hypereosinophilic syndromes (HES) that achieved glucocorticoid responsiveness defined as final minimally effective dose of prednisone of 0mg-15mg	Participants with hypereosinophilic syndromes (HES) with suboptimal glucocorticoid responsiveness defined as achieving final minimally effective dose of prednisone of 16mg-40mg	Participants with hypereosinophilic syndromes (HES) that were not responsive to prednisone defined as no decline of absolute eosinophil count (AEC) below 1000/mm^3 after one week of prednisone 30 mg daily, followed by 2 days of prednisone 60 mg daily
Measure Participants	11	5	7
Count of Participants [Participants]	4 17.4%	3 NaN	3 NaN

Adverse Events

Time Frame	20 weeks
Arm/Group Title	Steroid Challenge
Arm/Group Description	A single oral dose of prednisone (1 mg/kg rounded to the nearest 5mg) was administered to all participants. The following day, participant began glucocorticoid therapy of prednisone 30 mg oral daily for one week followed by a standardized taper until a minimally effective dose was achieved or participant tapered to prednisone 5 mg oral daily.
All Cause Mortality
	Steroid Challenge
	Affected / at Risk (%)	# Events
Total	0/23 (0%)
Serious Adverse Events
	Steroid Challenge
	Affected / at Risk (%)	# Events
Total	0/23 (0%)
Other (Not Including Serious) Adverse Events
	Steroid Challenge
	Affected / at Risk (%)	# Events
Total	7/23 (30.4%)
Eye disorders
Glaucoma	1/23 (4.3%)
Vitreous floaters	1/23 (4.3%)
General disorders
Swelling face	1/23 (4.3%)
Thirst	1/23 (4.3%)
Investigations
Weight increased	2/23 (8.7%)
Metabolism and nutrition disorders
Fluid retention	1/23 (4.3%)
Increased appetite	2/23 (8.7%)
Nervous system disorders
Dizziness	1/23 (4.3%)
Headache	1/23 (4.3%)
Psychiatric disorders
Insomnia	1/23 (4.3%)
Renal and urinary disorders
Polyuria	1/23 (4.3%)
Skin and subcutaneous tissue disorders
Dermatitis acneiform	1/23 (4.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.