Parathyroid Hormone (1-34)-Coated Microneedle Patch System: Clinical Pharmacokinetics and Pharmacodynamics for Treatment of Osteoporosis

• Published in: Pharmaceutical research Vol. 28; no. 1; pp. 159 - 165
• Main Authors: Daddona, Peter E, Matriano, James. A, Mandema, Jaap, Maa, Yuh-Fun
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01.01.2011; Springer US; Springer Nature B.V
• Subjects: Adult; Aged; Aged, 80 and over; Bioavailability; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Bone Density Conservation Agents - administration & dosage; Bone Density Conservation Agents - pharmacokinetics; Bone Density Conservation Agents - therapeutic use; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Delivery Systems - adverse effects; Drug Delivery Systems - instrumentation; Drug Delivery Systems - methods; Equipment Design; Female; Hormones; Humans; Injections, Intradermal; Macroflux; Medical Law; Microinjections - adverse effects; Microinjections - instrumentation; Microinjections - methods; Middle Aged; Needles; osteoporosis; Osteoporosis, Postmenopausal - drug therapy; parathyroid hormone; Pharmaceutical sciences; pharmacokinetics; pharmacology; Pharmacology/Toxicology; Pharmacy; PTH (1-34); Research Paper; teriparatide; Teriparatide - administration & dosage; Teriparatide - pharmacokinetics; Teriparatide - therapeutic use; Time Factors; Tissue Distribution; Transdermal medication; transdermal microneedle patch; Treatment Outcome; Macroflux; Parathyroid hormone; pharmacodynamics; pharmacokinetics; transdermal microneedle patch; teriparatide; osteoporosis; PTH (1-34)
• ISSN: 0724-8741; 1573-904X; 1573-904X
• DOI: 10.1007/s11095-010-0192-9

Objectives To evaluate the clinical PK/PD of PTH(1-34) delivered by a novel transdermal drug-coated microneedle patch system (ZP-PTH) for the treatment of osteoporosis. Methods Phase 1 PK studies evaluated the effect of site of administration, patch wear time and dose in normal volunteers, ages 40-85 yrs. Phase 2 was conducted in post-menopausal women with osteoporosis to determine the patch dose response compared to placebo patch and FORTEO® injection. Results Phase 1 ZP-PTH patch delivery demonstrated a rapid PTH plasma pulse profile with Tmax 3 times shorter and apparent T₁/₂ 2 times shorter than FORTEO®. In Phase 2, ZP-PTH 20, 30 and 40 µg doses showed a proportional increase in plasma PTH AUC. Inter-subject and intra-subject AUC variability was similar for all patch doses and comparable to injection. All patch doses produced a significant increase in spine bone mineral density. Unexpectedly, ZP-PTH also produced an early increase in hip bone mineral density, an effect not observed with the injection. Conclusions These studies suggest that this novel ZP-PTH patch system can deliver a consistent and therapeutically relevant PTH PK profile. Based on encouraging Phase 2 safety and efficacy data, the program is advancing into a pivotal Phase 3 clinical study.