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Pharmacokinetic Study of CYCLOSET ® 0.8 mg Tablets in Children and Adolescent Type 2 Diabetes Mellitus Subjects

Primary Purpose

Type 2 Diabetes

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Bromocriptine mesylate
Sponsored by
VeroScience
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Type 2 Diabetes focused on measuring Type 2 Diabetes, Children, Adolescents, Bioavailability, Cycloset, Bromocriptine Mesylate

Eligibility Criteria

10 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Availability for entire study and willingness to adhere to protocol requirements as evidenced by (ICF) duly read, signed and dated by the patient and responsible parent or guardian
  • Positive diagnosis of T2DM according to ADA criteria. There is no requirement for time since diagnosis as long as ADA guidelines have been followed.
  • Aged at least 10 years but less than 18 years at time of enrollment
  • BMI greater than 80th percentile for age and sex and body weight equal to or greater than 50 kg
  • Clinical laboratory values within the laboratory's stated normal range - if not within this range, they must be without any clinical significance
  • Healthy according to the medical history, laboratory results and physical examination
  • Non- or ex-smokers (defined as someone who completely stopped smoking for at least 30 days before day 1 of this study).

Exclusion Criteria:

  • Evidence to indicate a diagnosis of Type 1 diabetes
  • Body weight less than 50 kilograms
  • Systolic blood pressure lower than 115mmHg or diastolic blood pressure lower than 68 mmHg
  • Significant history of hypersensitivity to bromocriptine mesylate, ondansetron, other ergot alkaloids or any related products, including excipients of the formulation as well as severe hypersensitivity reactions (like angioedema) to any drugs
  • Presence of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects
  • Serum aspartate aminotransferase (AST) greater than 3X ULN, and/or serum alanine aminotransferase (ALT) greater than 3X ULN, and/or serum total bilirubin greater than 2.0 mg/dL.
  • Calculated glomerular filtration rate less than 80 mL/min based on the Schwartz Formula
  • Presence or history of uncontrolled hypertension: systolic pressure greater than 145 mmHg and/or diastolic pressure greater than 95 mmHg, hypertensive disorders of pregnancy, hypertension post-partum and in the puerperium
  • History of surgery that may affect drug bioavailability, including but not limited to cholecystectomy
  • Presence of significant cardiovascular, pulmonary, hematologic, neurologic, psychiatric, endocrine, immunologic or dermatologic disease
  • Symptoms and/or history of serious psychiatric or psychotic disorders
  • Presence of significant heart disease or disorder according to ECG
  • Presence of malignancy, particularly pituitary gland malignancy and prolactinoma
  • Presence or history of migraine headache or syncope
  • Pregnant according to a positive serum pregnancy test or lactating
  • Females less then four months post-partum
  • Current history of illicit drug dependency, use or alcohol abuse (greater than 3 units of alcohol per day, intake of excessive alcohol, acute or chronic).
  • Use of drugs for the treatment of ADD and ADHD
  • Inhaled corticosteroid use other than as a rescue treatment in case of asthma attack. Use of oral glucocorticoids. Use of oral steroids within the 60 days prior to study entry.
  • Any clinically significant illness in the previous 28 days before day 1 of this study
  • Use of any cytochrome P450 (CYP) 3A4 enzyme-modifying drugs, including strong inhibitors of CYP 3A4 enzymes and strong inducers of CYP3A4 enzymes (such as barbiturates, carbamazepine, phenytoin and rifampin), in the previous 28 days before Day 1 of this study
  • Participation in another clinical trial or donation of 50 mL or more of blood in the previous 42 days before day 1 of this study
  • Donation of 500 mL or more of blood in the previous 56 days before Day 1 of this study, as well as donation in excess of 900 mL of blood over the previous 20 weeks
  • Positive urine screening of drugs of abuse
  • Positive results to HIV, HBsAg or anti-HCV tests

Sites / Locations

  • Hope Research Institute, Llc
  • Yale Center for Clinical Investigation
  • Columbus Clinical Services LLC
  • The Children's Mercy Hospital
  • Children's Hosptial of Philadelphia

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Bromocriptine mesylate (Cycloset)

Arm Description

Bromocriptine mesylate (Cycloset)

Outcomes

Primary Outcome Measures

Pharmacokinetics
The pharmacokinetic parameters of interest will be Cmax, AUCT and AUC∞ and Tmax. Other parameters including AUCT/∞, Kel, T½el,CL/F, and Vd, will be provided for information purposes.

Secondary Outcome Measures

Full Information

First Posted
January 23, 2014
Last Updated
August 26, 2016
Sponsor
VeroScience
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1. Study Identification

Unique Protocol Identification Number
NCT02078440
Brief Title
Pharmacokinetic Study of CYCLOSET ® 0.8 mg Tablets in Children and Adolescent Type 2 Diabetes Mellitus Subjects
Official Title
Single Dose Pharmacokinetic Study of CYCLOSET ® 0.8 mg Tablets Following Administration of a Weight-Adjusted Dose in Male and Female Children and Adolescent Type 2 Diabetes Mellitus Subjects VS-PEDS BA-2010-V4
Study Type
Interventional

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
January 2014 (undefined)
Primary Completion Date
June 2016 (Actual)
Study Completion Date
June 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
VeroScience

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The objective of this study is to evaluate the relative bioavailability, and the rate and extent of absorption of bromocriptine in male and female children and adolescent Type 2 Diabetes Mellitus patients, aged 10 to less than 18, under fed conditions. It is undetermined if the pharmacokinetic profile of bromocriptine-QR in type 2 diabetes children aged 10- to less than 18 years differs appreciably from that in healthy adults. Bromocriptine is extensively metabolized by the liver (namely CYP3A4). Studies in children have demonstrated little difference in clearance among children over 10 years of age compared to adults (Blanco et al, 2000). However, differences in blood volumes or other factors may impart differences that could affect the pharmacokinetic properties of bromocriptine-QR. Therefore, this study will assess the pharmacokinetics in children aged 10-to less than 18 years who have type 2 diabetes. After describing the profile of bromocriptine-quick release in this patient population, a follow on study will be conducted to evaluate its safety and efficacy in treating children and adolescents who have type 2 diabetes. The pharmacokinetic profile of bromocriptine will be determined following the administration of a single, weight-adjusted dose of CYCLOSET (bromocriptine mesylate) tablets. The study will be a single period, bioavailability study in 30 patients. The study duration will be 3 days.
Detailed Description
The study is a multi-center, single dose, open-label, 1-period design. Thirty (30) patients will be enrolled in the study and at least twenty-four (24) patients are expected to complete the study. Male and female patients with confirmed Type 2 Diabetes, non-or ex-smokers, aged 10 to less than 18 years will be selected according to the inclusion and exclusion criteria. Patients will be admitted to the clinical site at least 10 hours prior to drug administration which will occur within 2 hours of waking on the morning of Day 2. Ondansetron hydrochloride will be administered orally, approximately 6 hours before the dosing time of Cycloset (bromocriptine mesylate). Subjects weighing 50 to 60 kg will receive 6mg ondansetron hydrochloride (liquid 7.5 ml) and subjects weighing ≥60 kg will receive ondansetron hydrochloride 8 mg (liquid 10 ml). A single, weight-adjusted dose of CYCLOSET (bromocriptine mesylate), of approximately 0.048 mg/kg, will be administered orally with 240 mL of water in the morning, after a 10-hour overnight fast, and thirty minutes after the start of a standardized breakfast that meets American Diabetes Association diet recommendations. On day 2, after a supervised overnight fast, the patients will be awakened, vital signs (blood pressure, pulse rate and body temperature) will be measured and the first blood sample (T= 0) will be collected. Seventeen (17) blood samples will be collected for pharmacokinetic sampling at 0.25, 0.50, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 16, 24 and 36 hours post drug administration. Finger sticks for blood glucose levels will be obtained every hour for the first 4 hours following administration of bromocriptine mesylate, and then additionally as deemed necessary by the study physician. Safety will be evaluated through the assessment of adverse events and laboratory tests and vital signs.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type 2 Diabetes
Keywords
Type 2 Diabetes, Children, Adolescents, Bioavailability, Cycloset, Bromocriptine Mesylate

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bromocriptine mesylate (Cycloset)
Arm Type
Other
Arm Description
Bromocriptine mesylate (Cycloset)
Intervention Type
Drug
Intervention Name(s)
Bromocriptine mesylate
Other Intervention Name(s)
Cycloset, Bromocriptine-QR, BQR
Intervention Description
Cycloset (bromocriptine mesylate quick release) 0.8 mg tablets, weight adjusted 1.6 mg- 4.8 mg
Primary Outcome Measure Information:
Title
Pharmacokinetics
Description
The pharmacokinetic parameters of interest will be Cmax, AUCT and AUC∞ and Tmax. Other parameters including AUCT/∞, Kel, T½el,CL/F, and Vd, will be provided for information purposes.
Time Frame
Thirty-six hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Availability for entire study and willingness to adhere to protocol requirements as evidenced by (ICF) duly read, signed and dated by the patient and responsible parent or guardian Positive diagnosis of T2DM according to ADA criteria. There is no requirement for time since diagnosis as long as ADA guidelines have been followed. Aged at least 10 years but less than 18 years at time of enrollment BMI greater than 80th percentile for age and sex and body weight equal to or greater than 50 kg Clinical laboratory values within the laboratory's stated normal range - if not within this range, they must be without any clinical significance Healthy according to the medical history, laboratory results and physical examination Non- or ex-smokers (defined as someone who completely stopped smoking for at least 30 days before day 1 of this study). Exclusion Criteria: Evidence to indicate a diagnosis of Type 1 diabetes Body weight less than 50 kilograms Systolic blood pressure lower than 115mmHg or diastolic blood pressure lower than 68 mmHg Significant history of hypersensitivity to bromocriptine mesylate, ondansetron, other ergot alkaloids or any related products, including excipients of the formulation as well as severe hypersensitivity reactions (like angioedema) to any drugs Presence of significant gastrointestinal, liver or kidney disease, or any other conditions known to interfere with the absorption, distribution, metabolism or excretion of drugs or known to potentiate or predispose to undesired effects Serum aspartate aminotransferase (AST) greater than 3X ULN, and/or serum alanine aminotransferase (ALT) greater than 3X ULN, and/or serum total bilirubin greater than 2.0 mg/dL. Calculated glomerular filtration rate less than 80 mL/min based on the Schwartz Formula Presence or history of uncontrolled hypertension: systolic pressure greater than 145 mmHg and/or diastolic pressure greater than 95 mmHg, hypertensive disorders of pregnancy, hypertension post-partum and in the puerperium History of surgery that may affect drug bioavailability, including but not limited to cholecystectomy Presence of significant cardiovascular, pulmonary, hematologic, neurologic, psychiatric, endocrine, immunologic or dermatologic disease Symptoms and/or history of serious psychiatric or psychotic disorders Presence of significant heart disease or disorder according to ECG Presence of malignancy, particularly pituitary gland malignancy and prolactinoma Presence or history of migraine headache or syncope Pregnant according to a positive serum pregnancy test or lactating Females less then four months post-partum Current history of illicit drug dependency, use or alcohol abuse (greater than 3 units of alcohol per day, intake of excessive alcohol, acute or chronic). Use of drugs for the treatment of ADD and ADHD Inhaled corticosteroid use other than as a rescue treatment in case of asthma attack. Use of oral glucocorticoids. Use of oral steroids within the 60 days prior to study entry. Any clinically significant illness in the previous 28 days before day 1 of this study Use of any cytochrome P450 (CYP) 3A4 enzyme-modifying drugs, including strong inhibitors of CYP 3A4 enzymes and strong inducers of CYP3A4 enzymes (such as barbiturates, carbamazepine, phenytoin and rifampin), in the previous 28 days before Day 1 of this study Participation in another clinical trial or donation of 50 mL or more of blood in the previous 42 days before day 1 of this study Donation of 500 mL or more of blood in the previous 56 days before Day 1 of this study, as well as donation in excess of 900 mL of blood over the previous 20 weeks Positive urine screening of drugs of abuse Positive results to HIV, HBsAg or anti-HCV tests
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bindu Chamarthi, MD MMSc
Organizational Affiliation
VeroScience
Official's Role
Study Director
Facility Information:
Facility Name
Hope Research Institute, Llc
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85018
Country
United States
Facility Name
Yale Center for Clinical Investigation
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06511
Country
United States
Facility Name
Columbus Clinical Services LLC
City
Miami
State/Province
Florida
ZIP/Postal Code
33165
Country
United States
Facility Name
The Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Children's Hosptial of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

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Pharmacokinetic Study of CYCLOSET ® 0.8 mg Tablets in Children and Adolescent Type 2 Diabetes Mellitus Subjects

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