Clinical trial NCT00255502: 307B - Safety, Tolerability and Pharmacokinetics Study of TOPROL-XL® in Hypertensive Pediatric Subjects
Official title: A Safety, Tolerability and Pharmacokinetics Study of TOPROL-XL® (Metoprolol Succinate) Extended-release Tablets (Metoprolol CR/XL) in Hypertensive Pediatric Subjects: A Multicenter, Open-Label Extension of Protocol 307A
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Keywords: Pediatric hypertension
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2005-11-21
Enrollment: 100
Sex: ALL
Minimum age (years): 6
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This was a 52-week, multicenter, open-label study to determine the safety, tolerability and pharmacokinetics of TOPROL-XL (metoprolol succinate) extended-release tablets (metoprolol CR/XL) in hypertensive pediatric subjects. The study population included school age children (age 6 to 12 years \< Tanner Stage 3) and adolescents (\> 12 years old or \> Tanner Stage 3 to 16 years old) of both genders. Because response to some therapies in adult hypertension appears to be different in black and non-black populations, the recruitment will have a mixture of black and non-black subjects. Pharmacokinetic measurements were performed on a subset of patients. Thirty subjects (15 subjects each in the 6 to 12 year age group and the 13 to 16 year age group) had a series of blood samples drawn. All subjects had a trough plasma level taken 24 hours after the last dose of open-label metoprolol CR/XL (Visit 18) with the exception of those subjects who completed Protocol 307B (16 week open-label treatment).


Eligibility criteria: Inclusion Criteria:

* Male or female between the ages of 6 and 16 years inclusive at the time of screening.
* Have a negative urine pregnancy test, if female of childbearing potential. Have a signed informed consent by a parent or a legal guardian and an assent form signed by the subject (if applicable).
* Have hypertension that is either:

  1. Have successfully completed Protocol 307A, or, or
  2. Have dropped out of Protocol 307A or failed screening for Protocol 307A for sitting SBP/DBP greater than 20/10 mm Hg over the 95 th percentile using height adjusted charts for age and gender (see Appendices B through E inclusive), or
  3. Have not enrolled in Protocol 307A but meet all screening criteria for Protocol 307B and are enrolled at sites that have already randomized 6 subjects into Protocol 307A.
* Have the ability to swallow tablets.

Exclusion Criteria:

* Have secondary hypertension due to coarctation of aorta, pheochromocytoma, hyperthyroidism or Cushing's syndrome.
* Have a heart rate \< 55 beats per minute at Visit 1.
* Have a history of asthma and/or recurring pulmonary disease or infections.
* Have a history of cystic fibrosis.
* Have a known hypersensitivity reaction to beta-blockers.
* Have a known bleeding, coagulation or platelet disorder that can interfere with blood sampling.
* Have a history of Insulin Dependent Diabetes Mellitus.
* Be in any situation or have any condition which, in the opinion of the investigator or sponsor, may interfere with participation in the study or produce a significant risk to the subject or interfere with the assessment of safety and efficacy endpoints.
* Have received any investigational agent for any therapeutic reason within 30 days prior to receiving study medication.
* Have a clinically significant cardiac valvular disease.
* Have a diagnosis of heart failure.
* Have clinically significant arrhythmia. This is defined as any arrhythmia requiring medical therapy or that causes symptoms.
* Atrioventricular (AV) conduction disturbance, ie, second or third degree AV block.
* Be unable or unwilling to comply with the study requirements.
* Be non-compliant during the single-blind placebo run-in period of the study as defined by missing three or more doses between study visits.
* Have impaired liver function defined as either acute liver disease or chronic liver disease with persistent liver enzyme values greater than one and one half times the upper limit of the normal range for AST or ALT.
* Have a known history of bilateral renal artery stenosis, or unilateral renal artery stenosis to a single kidney. Nephrotic subjects who are not in remission should be excluded.
* Be pregnant or breast-feeding an infant.
* Currently taking medications known to inhibit CYP2D6, such as quinidine, fluoxetine, paroxetine and propafenone.
* Currently taking catecholamine-depleting medications such as reserpine. For any subject who is currently taking medications known to inhibit CYP2D6 or any catecholamine-depleting medication, the sponsor must be contacted to assess feasibility for inclusion into the study.
* Currently taking any selective serotonin re-uptake inhibitors (SSRIs) or atypical antipsychotic medication.
* Have a history of alcohol or drug abuse, or have a positive urine screen for drugs of abuse or alcohol.

Primary outcomes:
measure: The purpose of this trial is to evaluate the pharmacokinetics and long term safety and
measure: tolerability of metoprolol CR/XL in hypertensive pediatric subjects.
Secondary outcomes:
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Bellflower
country: United States
facility: Research Site
state: California
city: Beverly Hills
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: Hartford
country: United States
facility: Research Site
state: Connecticut
city: Wilmington
country: United States
facility: Research Site
state: Delaware
city: Gainesville
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Honolulu
country: United States
facility: Research Site
state: Hawaii
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Livingston
country: United States
facility: Research Site
state: New Jersey
city: Bronx
country: United States
facility: Research Site
state: New York
city: New Hyde Park
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Lansdale
country: United States
facility: Research Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Greenville
country: United States
facility: Research Site
state: South Carolina
city: Beaumont
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Norfolk
country: United States
facility: Research Site
state: Virginia
city: Santa Domingo
country: Dominican Republic
facility: Research Site
Study officials:
affiliation: AstraZeneca
name: AstraZeneca Toprol Medical Science Director, MD
role: STUDY_DIRECTOR
References:
citation: Batisky DL, Sorof JM, Sugg J, Llewellyn M, Klibaner M, Hainer JW, Portman RJ, Falkner B; Toprol-XL Pediatric Hypertension Investigators. Efficacy and safety of extended release metoprolol succinate in hypertensive children 6 to 16 years of age: a clinical trial experience. J Pediatr. 2007 Feb;150(2):134-9, 139.e1. doi: 10.1016/j.jpeds.2006.09.034.