title: Intranasal Human Growth Hormone (hGH) Induces IGF-1 Levels Comparable With Subcutaneous Injection With Lower Systemic Exposure to hGH in Healthy Volunteers.
abstract: BACKGROUND
  The development of an improved, efficacious human GH (hGH) product administered by a noninjectable route of delivery such as the nasal route is highly desirable. We have developed a novel nasal hGH product (CP024) that showed excellent nasal absorption in animal models; however, the translation of these results into the clinical setting is essential because past attempts to develop such formulations by other groups have been unable to induce IGF-1 in man.
  
  
  OBJECTIVE
  The objective of the study was to assess the pharmacokinetics, pharmacodynamics, and tolerability of CP024 compared with a sc hGH injection.
  
  
  METHODS
  This was a single-center, nonrandomized placebo-controlled, open-label, five-way crossover study in eight healthy volunteers.
  
  
  METHODS
  The study was carried out at a contract research organization, Quotient Bioresearch.
  
  
  METHODS
  Eight healthy male volunteers, given an iv infusion of octreotide to suppress the endogenous GH secretion during the study period, participated in the study. No volunteers were withdrawn due to side effects.
  
  
  METHODS
  Measurement of hGH and IGF-1 levels and tolerability of the drug product was performed.
  
  
  RESULTS
  No serious adverse events were reported and no subjects withdrawn from study due to the treatment. After the nasal administration of CP024, 3-fold higher hGH blood levels were obtained as compared with hGH nasal control. The relative bioavailability was about 3%. CP024 (given twice daily) induced a significant increase in IGF-1 levels up to 19 hours after administration, with no significant difference to those obtained after the sc injection of hGH.
  
  
  CONCLUSIONS
  The study indicates that CP024 is a promising candidate for an efficacious nasal product for the treatment of GH deficiency due to induction of IGF-1 similar to that after a sc injection, despite the lower plasma hGH concentration obtained. A dose-response study is needed to evaluate the optimal nasal dose.
authors.affiliation: Critical Pharmaceuticals Ltd (A.L.L., F.J., T.P., K.J., G.K., L.I.), BioCity Nottingham, Nottingham NG1 1GF, United Kingdom; Department of Endocrinology (M.S.), William Harvey Research Institute, Barts and the Royal London School of Medicine and Dentistry, London E1 1BB, United Kingdom; and Department of Endocrinology (S.S.), Christie Hospital, Manchester M20 4BX, United Kingdom.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Lewis
authors.affiliation: Critical Pharmaceuticals Ltd (A.L.L., F.J., T.P., K.J., G.K., L.I.), BioCity Nottingham, Nottingham NG1 1GF, United Kingdom; Department of Endocrinology (M.S.), William Harvey Research Institute, Barts and the Royal London School of Medicine and Dentistry, London E1 1BB, United Kingdom; and Department of Endocrinology (S.S.), Christie Hospital, Manchester M20 4BX, United Kingdom.
authors.forename: Faron
authors.initials: F
authors.lastname: Jordan
authors.affiliation: Critical Pharmaceuticals Ltd (A.L.L., F.J., T.P., K.J., G.K., L.I.), BioCity Nottingham, Nottingham NG1 1GF, United Kingdom; Department of Endocrinology (M.S.), William Harvey Research Institute, Barts and the Royal London School of Medicine and Dentistry, London E1 1BB, United Kingdom; and Department of Endocrinology (S.S.), Christie Hospital, Manchester M20 4BX, United Kingdom.
authors.forename: Tina
authors.initials: T
authors.lastname: Patel
authors.affiliation: Critical Pharmaceuticals Ltd (A.L.L., F.J., T.P., K.J., G.K., L.I.), BioCity Nottingham, Nottingham NG1 1GF, United Kingdom; Department of Endocrinology (M.S.), William Harvey Research Institute, Barts and the Royal London School of Medicine and Dentistry, London E1 1BB, United Kingdom; and Department of Endocrinology (S.S.), Christie Hospital, Manchester M20 4BX, United Kingdom.
authors.forename: Kirk
authors.initials: K
authors.lastname: Jeffery
authors.affiliation: Critical Pharmaceuticals Ltd (A.L.L., F.J., T.P., K.J., G.K., L.I.), BioCity Nottingham, Nottingham NG1 1GF, United Kingdom; Department of Endocrinology (M.S.), William Harvey Research Institute, Barts and the Royal London School of Medicine and Dentistry, London E1 1BB, United Kingdom; and Department of Endocrinology (S.S.), Christie Hospital, Manchester M20 4BX, United Kingdom.
authors.forename: Gareth
authors.initials: G
authors.lastname: King
authors.affiliation: Critical Pharmaceuticals Ltd (A.L.L., F.J., T.P., K.J., G.K., L.I.), BioCity Nottingham, Nottingham NG1 1GF, United Kingdom; Department of Endocrinology (M.S.), William Harvey Research Institute, Barts and the Royal London School of Medicine and Dentistry, London E1 1BB, United Kingdom; and Department of Endocrinology (S.S.), Christie Hospital, Manchester M20 4BX, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Savage
authors.affiliation: Critical Pharmaceuticals Ltd (A.L.L., F.J., T.P., K.J., G.K., L.I.), BioCity Nottingham, Nottingham NG1 1GF, United Kingdom; Department of Endocrinology (M.S.), William Harvey Research Institute, Barts and the Royal London School of Medicine and Dentistry, London E1 1BB, United Kingdom; and Department of Endocrinology (S.S.), Christie Hospital, Manchester M20 4BX, United Kingdom.
authors.forename: Stephen
authors.initials: S
authors.lastname: Shalet
authors.affiliation: Critical Pharmaceuticals Ltd (A.L.L., F.J., T.P., K.J., G.K., L.I.), BioCity Nottingham, Nottingham NG1 1GF, United Kingdom; Department of Endocrinology (M.S.), William Harvey Research Institute, Barts and the Royal London School of Medicine and Dentistry, London E1 1BB, United Kingdom; and Department of Endocrinology (S.S.), Christie Hospital, Manchester M20 4BX, United Kingdom.
authors.forename: Lisbeth
authors.initials: L
authors.lastname: Illum
mesh_terms: D000281:Administration, Intranasal; D000328:Adult; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D064368:Healthy Volunteers; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000494:pharmacology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D015282:Octreotide