Efficacy and Safety of Cycloset® Compared With Placebo When Added to Metformin

• Sponsor: VeroScience (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00441363
• Collaborator: (none)
• Enrollment: 66
• Arms: 2
• Duration (Months): 12.9

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the efficacy and safety of Cycloset® and placebo when added to metformin monotherapy (at least 1000 mg/day for 3 months prior to screening) in persons with type 2 diabetes mellitus who are not adequately controlled on metformin therapy alone.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: Bromocriptine Mesylate	Phase 3

Detailed Description

In the previously conducted Phase III clinical trials, Cycloset® (up to a maximum dose of 4.8 mg/day), administered either as monotherapy or combined with sulfonylurea therapy, significantly reduced HbA1c, fasting and post-prandial glucose and fasting and post-prandial triglycerides in obese individuals with type 2 diabetes mellitus. Clinical studies that combined Cycloset® with metformin were not as part of the original Cycloset® clinical program because metformin was not commercially available in the United States at the time that the studies were initiated. The present study is designed to investigate the efficacy and safety of Cycloset® compared to placebo when added to metformin monotherapy in persons with type 2 diabetes mellitus who are not adequately controlled on metformin therapy alone.

A sufficient number of individuals will be screened to enroll up to 326 subjects;approximately 276 subjects are expected to complete treatment through study termination (Week 26). The study population will consist of individuals currently treated with metformin, for at least 3 months prior to the study start. Subjects who have ever received exogenous insulin therapy as part of an outpatient diabetes treatment regimen are to be excluded, as are those taking oral anti-diabetic agents other than metformin within 3 months of screening (e.g., sulfonylureas, thiazolidinediones,alpha-glucosidase inhibitors, or meglitinides). Subjects may be male or female(surgically sterile, postmenopausal, or using appropriate contraceptive methods if of childbearing potential), age 18 to 75 years, inclusive, and are to have a screening HbA1c value of ≥ 7.5% and <11.0% and a screening body mass index (BMI) in the range of 25 kg/m2 to 42 kg/m2, inclusive.

Study Design

• Study Type: Interventional
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Parallel-Group Trial to Assess the Efficacy and Safety of Cycloset® Compared With Placebo When Added to Metformin in Patients With Type 2 Diabetes Mellitus
• Study Start Date: Feb 1, 2005
• Actual Primary Completion Date: Feb 1, 2006
• Actual Study Completion Date: Mar 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Bromocriptine Mesylate Bromocriptine mesylate 0.8 mg	Drug: Bromocriptine Mesylate; 0.8 mg tablet; Other Names: Cycloset
Placebo Comparator: Placebo Bromocriptine mesylate 0.8 mg matching placebo	Drug: Bromocriptine Mesylate; 0.8 mg tablet; Other Names: Cycloset

Outcome Measures

Primary Outcome Measures

1. Change in Baseline to End of Study in HbA1c [up to 24 weeks]

   Too few subjects were enrolled to assess outcome to pre-specified statistical power.

Secondary Outcome Measures

1. Fasting Plasma Glucose and Lipids [up to 24 weeks]

2. Number of Serious Adverse Events Experienced by the Subjects [up to 24 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Diagnosed with type 2 diabetes mellitus, for at least six months prior to screening.

2. 18-75 years of age, inclusive.

3. Male or if female, is either:

• postmenopausal or

• of childbearing potential and has used appropriate contraceptive methods

1. Treated with a stable dose of metformin at least 3 months.

2. Has not been treated with a sulfonylurea, thiazolidinedione, meglitinide, alpha-glucosidase inhibitor, or combination oral anti-diabetic therapy within 3 months prior to screening.

3. Has not been on a regimen of lipid-lowering agents or if on such a regimen, it has been stable for a minimum of 6 weeks at screening.

4. HbA1c value between ≥ 7.5% and < 11%, at screening (Visit 1) and Visit 3.

5. Fasting plasma glucose measurement of ≤260 mg/dL at screening (Visit 1) and Visit 3.

6. Fasting C-peptide value equal to or greater than the normal accepted minimum value (e.g. < 0.9 NG/ml).

7. Stable body weight, i.e., not varying by > 10% for at least3 months prior to screening

8. Body mass index (BMI) at screening of 25 kg/m2 to 42 kg/m2,inclusive.

9. If treated for hypertension, the individual has been on stable therapy for 1 month prior to screening.

Exclusion Criteria:

1. Prior exogenous insulin therapy as part of an outpatient diabetes treatment regimen.

2. Type 1 diabetes mellitus

3. Clinically significant history of cardiac disease or presence of cardiac disease, including MI, clinically significant arrhythmia, unstable angina pectoris, moderate to severe congestive heart failure, CABG, or angioplasty; or expected to require CABG or angioplasty during the study.

4. Uncontrolled hypertension, defined as systolic blood pressure > 160 or diastolic blood pressure > 100 mmHg measured in sitting position at screening(Visit 1)

Clinically significant history or presence of:

1. Hepatic disease (i.e. impaired liver function, including having AST or ALT greater than three times the upper limit of normal)

2. Renal disease (i.e. renal impairment with a serum creatinine ≥ 1.4 mg/dl)

3. Central nervous system disease, including epilepsy

4. CVA within the last 3 years.

5. Less than 5 years remission from clinically significant malignancy.

6. Major surgical operation within 3 months of screening.

7. Organ transplantation.

8. Evidence of acute or chronic illness including known or suspected HIV,HBV, or HCV infection.

9. Currently abuses drugs or alcohol, including binge drinking, or history of abuse that in the investigator's opinion would cause the individual to be noncompliant.

10. Regularly uses medications with addictive potential such as opiates,narcotics, tranquilizers, etc.

11. Used drugs for weight loss, e.g., Xenical® (orlistat), Meridia® (sibutramine),Acutrim® (phenylpropanolamine), or similar over-the-counter medications within 3 months of screening.

12. Known hypersensitivity to any components of the study drugs.

13. Received any experimental drug or used an experimental device within 3 months of screening or will do so during the study.

14. Has received unstable dose of fibric acid derivatives within 3 months of the screening.

15. Requires regular use of systemic corticosteroids by oral, intravenous (IV),or intramuscular (IM) route, or regular use of potent, inhaled intranasal steroids that are known to have a high rate of systemic absorption.

16. Prescription sympathomimetic drugs within 7 days of screening.

17. Started therapy with an erectile dysfunction drug within 2 weeks prior to screening. The subject may not begin treatment with an erectile dysfunction drug during the study period; subjects previously taking erectile dysfunction drugs should do so only under medical supervision.

18. Donated blood within 60 days of screening. Donation of blood also is prohibited during the study and for 30 days after completion of the study.

19. Occupation that requires a rotation of shift work or working over night shifts.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• VeroScience

Investigators

• Study Director: Richard E Scranton, MD, VeroScience

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: VeroScience
• ClinicalTrials.gov Identifier: NCT00441363
• Other Study ID Numbers: 165-AD-04-03-US-2
• First Posted: Feb 28, 2007
• Last Update Posted: May 9, 2016
• Last Verified: Apr 1, 2016

• Keywords provided by VeroScience: diabetes; diabetes mellitus
• Additional relevant MeSH terms: Diabetes Mellitus, Type 2; Bromocriptine

Study Results

Participant Flow

Recruitment Details	The study was originally designed to enroll 326 subjects in order to randomize 225 subjects. Due to a strategic business decision of the former sponsor (PLIVA), enrollment into the study was prematurely terminated.

Arm/Group Title	Cycloset	Placebo
Arm/Group Description	0.8 mg tablet	matching placebo
Period Title: Overall Study
STARTED	32	34
COMPLETED	15	19
NOT COMPLETED	17	15

Baseline Characteristics

Arm/Group Title	Cycloset	Placebo	Total
Arm/Group Description	0.8 mg tablet	matching placebo	Total of all reporting groups
Overall Participants	32	34	66
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54 (10.5)	53 (9.3)	53 (9.8)
Sex: Female, Male (Count of Participants)
Female	15 46.9%	14 41.2%	29 43.9%
Male	17 53.1%	20 58.8%	37 56.1%
Region of Enrollment (participants) [Number]
United States	32 100%	34 100%	66 100%

Outcome Measures

1. Primary Outcome

Title	Change in Baseline to End of Study in HbA1c
Description	Too few subjects were enrolled to assess outcome to pre-specified statistical power.
Time Frame	up to 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cycloset	Placebo
Arm/Group Description	0.8 mg tablet	matching placebo
Measure Participants	32	34
Mean (Standard Deviation) [% HbA1c]	-0.4 (.95)	-.5 (0.87)

2. Secondary Outcome

Title	Fasting Plasma Glucose and Lipids
Time Frame	up to 24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	Number of Serious Adverse Events Experienced by the Subjects
Time Frame	up to 24 weeks

Outcome Measure Data

Analysis Population Description

Report of Serious adverse events that occurred in the trial.

Arm/Group Title	Cycloset	Placebo
Arm/Group Description	0.8 mg tablet	matching placebo
Measure Participants	32	34
Number [serious adverse events]	1	0

Adverse Events

Arm/Group Title	Cycloset		Placebo
Arm/Group Description	0.8 mg tablet		matching placebo
All Cause Mortality
	Cycloset		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cycloset		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/32 (3.1%)		0/34 (0%)
Cardiac disorders
unstable angina	1/32 (3.1%)	1	0/34 (0%)	0
Other (Not Including Serious) Adverse Events
	Cycloset		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/32 (62.5%)		14/34 (41.2%)
Eye disorders
Vision blurred	2/32 (6.3%)		0/34 (0%)
Gastrointestinal disorders
nausea	6/32 (18.8%)		3/34 (8.8%)
vomiting	3/32 (9.4%)		2/34 (5.9%)
General disorders
Fatigue	2/32 (6.3%)		0/34 (0%)
Infections and infestations
Urinary Tract Infection	2/32 (6.3%)		0/34 (0%)
Sinusitis	1/32 (3.1%)		2/34 (5.9%)
Nasopharyngitis	1/32 (3.1%)		2/34 (5.9%)
Musculoskeletal and connective tissue disorders
Pain in extremity	2/32 (6.3%)		2/34 (5.9%)
back pain	2/32 (6.3%)		1/34 (2.9%)
Nervous system disorders
Dizziness	2/32 (6.3%)		2/34 (5.9%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/32 (6.3%)		0/34 (0%)

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.