Study of an Extended-Release, Crystalline Formulation of Recombinant Human Growth Hormone (ALTU-238) in Growth Hormone Deficient Adults to Determine Pharmacokinetics, Pharmacodynamics, and Drug Safety

A Phase II, Multi-Center, Multi-Dose, Randomized, Open-Label, Parallel Group Study of an Extended-Release, Crystalline Formulation of Recombinant Human Growth Hormone (ALTU-238) in Growth Hormone Deficient Adults to Determine Pharmacokinetics, Pharmacodynamics, and Drug Safety

ALTU-238 is a long acting crystalline formulation of recombinant human growth hormone (rhGH) that is being developed for the treatment of growth hormone deficiency in adults and children. ALTU-238 is designed to require fewer injections than the currently available formulations of rhGH.

Inclusion Criteria:

• Growth hormone deficient men and women ages 18-60 years with a hypothalamic and/or pituitary structural lesion or longstanding idiopathic GHD

• Growth hormone deficiency as determined by pituitary testing within the last five years by either of the two following tests:

  1. Insulin hypoglycemia (glucose < 50 mg/dL) with maximum GH < 5 ng/mL (5 µg/L) by radioimmunoassay or < 2.5 µg/L, if measured by immunoradiometric assay
  2. Arginine-GHRH infusions with maximum GH < 5 ng/mL (5 µg/L) or < 2.5 µg/L, if measured by immunoradiometric assay

• Women must be of non-child bearing potential (hysterectomy, tubal ligation, or IUD are acceptable) during the three months prior to entering the study, or post-menopausal (no menses for one year or more), or six to twelve months without menses and β-estradiol levels < 20 pg/mL

• Glucocorticoid use is allowed provided the subject has been on physiologic (<7.5 mg prednisone or equivalent/day) replacement doses for at least 3 months

• Free thyroxine (T4) within the normal range at Screening. If the subject is receiving thyroid hormone replacement therapy, the dose must be stable for at least 6 weeks prior to Screening

• Willing and able to provide written informed consent

• BMI 20 - 36 kg/m2

Exclusion Criteria:

• Any previous or ongoing clinically significant illness that, in the opinion of the investigator, could prevent the subject from completing the study
• Any history of cancer within the past 5 years, except for dermal squamous and basal cell carcinoma with documented 6-month remission. Subjects with a more recent history of successfully treated cervical carcinoma in situ will not be excluded provided there is documented 12-month remission
• BMI <20 or >36 kg/m2
• Any allergic or abnormal reaction to human growth hormone
• Inability of the subject to discontinue use of their regularly prescribed human growth hormone treatment from six weeks prior to Day -1 through the completion of the study
• Serum creatinine > 1.4 mg/dL
• Hypocalcemia or hypercalcemia from any cause
• Hyperparathyroidism, osteomalacia or any other disorder which may affect bone and bone markers including the use of bisphosphonates or other medications for osteoporosis
• Participation in another clinical trial 30 days prior to screening
• Demonstrated inability to comply with protocol requirements (e.g. uncooperative attitude, inability to return for follow-up visits, history of medical non-compliance, and/or poor likelihood of completing the study)
• Blood donation within 56 days of the screening visit
• Plasma donation within seven days of the screening visit
• Positive serum pregnancy test
• Women of child bearing potential
• Abuse of alcohol; to be determined by principal investigator
• Abuse of prescription or illicit drugs; to be determined by principal investigator