title: First-in-human testing of a wirelessly controlled drug delivery microchip.
abstract: The first clinical trial of an implantable microchip-based drug delivery device is discussed. Human parathyroid hormone fragment (1-34) [hPTH(1-34)] was delivered from the device in vivo. hPTH(1-34) is the only approved anabolic osteoporosis treatment, but requires daily injections, making patient compliance an obstacle to effective treatment. Furthermore, a net increase in bone mineral density requires intermittent or pulsatile hPTH(1-34) delivery, a challenge for implantable drug delivery products. The microchip-based devices, containing discrete doses of lyophilized hPTH(1-34), were implanted in eight osteoporotic postmenopausal women for 4 months and wirelessly programmed to release doses from the device once daily for up to 20 days. A computer-based programmer, operating in the Medical Implant Communications Service band, established a bidirectional wireless communication link with the implant to program the dosing schedule and receive implant status confirming proper operation. Each woman subsequently received hPTH(1-34) injections in escalating doses. The pharmacokinetics, safety, tolerability, and bioequivalence of hPTH(1-34) were assessed. Device dosing produced similar pharmacokinetics to multiple injections and had lower coefficients of variation. Bone marker evaluation indicated that daily release from the device increased bone formation. There were no toxic or adverse events due to the device or drug, and patients stated that the implant did not affect quality of life.
authors.affiliation: MicroCHIPS, Inc., Waltham, MA 02451, USA. rfarra@mchips.com
authors.forename: Robert
authors.initials: R
authors.lastname: Farra
authors.forename: Norman F
authors.initials: NF
authors.lastname: Sheppard
authors.forename: Laura
authors.initials: L
authors.lastname: McCabe
authors.forename: Robert M
authors.initials: RM
authors.lastname: Neer
authors.forename: James M
authors.initials: JM
authors.lastname: Anderson
authors.forename: John T
authors.initials: JT
authors.lastname: Santini
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cima
authors.forename: Robert
authors.initials: R
authors.lastname: Langer
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002214:Capsules; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000009:adverse effects / Q000295:instrumentation* / Q000379:methods*; D005260:Female; D006801:Humans; D056656:Lab-On-A-Chip Devices; D019379:Teriparatide / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D059015:Wireless Technology / Q000295:instrumentation*
chemical_list: D015415:Biomarkers; D002214:Capsules; D019379:Teriparatide; D002118:Calcium