Efficacy and Safety of Phentermine/Topiramate in Youth With Hypothalamic Obesity

Korábbi kezelés

• Current or recent (<14 days) use of monoamine oxidase inhibitor.
• History of seizure in the 12 months prior to Screening.
• Current use of supra-physiologic steroids.
• Concurrent use of carbonic anhydrase inhibitors.
• New weight management medication (or >5% decrease in weight over prior 2 months on any current, stable regimen), stimulant, and/or investigational medication within 2 months prior to screening, and/or plans to initiate other new weight management regimen.

Más betegség

• Contraindication to Phentermine, Topiramate, or Qsymia as assessed using current package inserts. Including: History of glaucoma and known hyperthyroidism.
• Known history of nephrolithiasis (kidney stones).
• Known hypersensitivity to sympathomimetic amines.
• History of substance abuse, depression of moderate or greater severity, psychiatric disorder and/or suicidality.
• History of abdominal surgery including gastric bypass.
• History of allergy or sensitivity to test agents. Including individuals with known aspirin allergy or hypersensitivity and/or known allergy to FD\&C Yellow No. 5 (tartrazine).
• Cognitive impairment that, in the opinion of the investigator, precludes participation in the study.

Laborértékek

• Known history of metabolic acidosis, low bicarbonate on screening laboratory assessment (below lower limit of normal), or clinically significant bone disease requiring medication (beyond calcium and/or vitamin D).
• Clinically significant cardiovascular conditions, as defined as any of the following: i) abnormal blood pressure, defined as: under 13y, 95th%ile +12 mm Hg or > 140/90, whichever is lower; 13y and older, > 140/90 ; ii) history of cardiac arrhythmia or arrhythmia detected on screening ECG; iii) history of heart failure and/or cardiomyopathy; iv) prolonged QTc interval (QTc > 460 msec), and/or long QT syndrome phenotype and/or positive genotype for long QT syndrome pathogenic; v) history of cardiac disease including coronary artery disease.
• "Brittle" diabetes insipidus (in the opinion of the referring endocrinologist, e.g. requiring frequent hospitalizations and/or frequent abnormal sodium values).
• Diabetes mellitus requiring insulin/secretagogue. HbA1c > 8.5% at Screening.
• History of clinically significant hypokalemia (low potassium) or current clinically significant hypokalemia (low potassium) on baseline/screening labs.
• Clinically significant liver disease and/or known severe hepatic impairment. ALT > 3 x Upper Limit of Normal (ULN) AST > 3 x ULN
• Clinically significant kidney disease. GFR<60 ml/min/1.73m2
• Concurrent use of non-potassium sparing diuretics.

Egyéb

• Current clinical diagnosis of anorexia nervosa or bulimia nervosa in the medical record.
• Females who are pregnant, breastfeeding, or planning to become pregnant during the trial.
• Clinically significant hyperthyroidism as assessed using thyroid hormone measurements. Clinical measurements within 12 months of baseline/screening may be used to assess this criterion.
• Individuals considered, in the Investigator's opinion, not suitable to participate in the study for reasons other than those indicated above.

• Males and Females; Ages 6-28 years (inclusive)
• History of rapid weight gain related to tumor onset or treatment, as assessed by an experienced endocrinologist (for example, change in BMI z-score > 0.2 and/or BMI +5% during the first 6 months following tumor treatment)
• Obesity (BMI > 95th%ile for age/sex using CDC 2000 reference for under 18; BMI > 30 kg/m2 for 18+ years)
• Recent evidence of hypothalamic injury by brain MRI with central review; >6 months status-post definitive therapy (surgery, chemotherapy, or radiation); no major operations/surgeries planned during the study period.
• Stable on pituitary replacement* and/or appetite-modulating medications (including stimulants) for at least 2 months. *Adjustments of less than 25% (<25%) are permitted to hydrocortisone, growth hormone or thyroid hormone. Sex steroids and DDAVP are exempt.
• Post-menarchal females must use a highly effective form of contraception, unless hypogonadotropic hypogonadism is documented. All participating females of child-bearing potential will have pregnancy testing as outlined in the protocol.
• Participants must be able to communicate well with the investigative team, must comply with requirements of the study, and be able to provide written informed consent and/or assent for individuals less than 18y with consent of a parent/legal guardian.