Parathyroid hormone (1-34)-coated microneedle patch system: clinical pharmacokinetics and pharmacodynamics for treatment of osteoporosis.
OBJECTIVE
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 T(max) 3 times shorter and apparent T(1/2) 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.
Daddona
Peter E
PE
Zosano Pharma, Inc., 34790 Ardentech Court, Fremont, California 94555, USA. pdaddona@zosanopharma.com
Matriano
James A
JA
Mandema
Jaap
J
Maa
Yuh-Fun
YF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D004867:Equipment Design; D005260:Female; D006801:Humans; D007271:Injections, Intradermal; D008845:Microinjections / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D008875:Middle Aged; D009339:Needles; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D019379:Teriparatide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D013997:Time Factors; D014018:Tissue Distribution; D016896:Treatment Outcome
D050071:Bone Density Conservation Agents; D019379:Teriparatide