A Phase I Study of AK159 in Healthy Postmenopausal Women

Study Overview
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Brief Summary
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The objective of this study is to investigate the pharmacokinetics, safety, and tolerability of AK159 administered to healthy postmenopausal women.

Detailed Description
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This study consists of two parts: Part 1 and Part 2. The Part 1 is a single-center, randomized, 2-way crossover study that investigates the pharmacokinetics, safety, and tolerability of teriparatide after a single dose of AK159 (5 levels) and estimates the relative bioavailability of AK159 with subcutaneous teriparatide acetate in healthy post-menopausal women. The Part 2 is a multiple-center, randomized, double-blind, positive- and placebo-controlled, parallel study that compares the pharmacokinetics, bone makers, safety, and tolerability of teriparatide after a weekly doses of AK159 (4 levels) for 6 weeks with placebo and a weekly doses of subcutaneous teriparatide acetate in healthy post-menopausal women.

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: AK159
* Drug: MN-10-T
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy postmenopausal ethnic Japanese women At least 45 years of age at the time consent is obtained Give voluntary consent in writing with a sufficient understanding of the study. Exclusion Criteria: Clinical abnormality identified in the laboratory tests Weight < 40.0 kg Body mass index < 17.5 or >=30.5 History of disease of the kidneys, liver, heart, brain, or other organ that makes them ineligible as subjects Previously received radiation treatment potentially affecting bone Clinical abnormality identified in the 12-lead ECGs performed at the study center during the screening period Systolic blood pressure < 90 mmHg Serum calcium level exceeding 10.4 mg/dL History of contact dermatitis or skin disease potentially compromising study evaluation Used drugs which impact bone metabolism in the 8-week period preceding investigational product administration Used a bisphosphonate Used a teriparatide product

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK159 SD 1<br>Single administration of AK159 dose level 1 | Drug: AK159<br>* transdermal administration of teriparatide acetate<br>|
| Experimental: AK159 SD 2<br>Single administration of AK159 dose level 2 | Drug: AK159<br>* transdermal administration of teriparatide acetate<br>|
| Experimental: AK159 SD 3<br>Single administration of AK159 dose level 3 | Drug: AK159<br>* transdermal administration of teriparatide acetate<br>|
| Experimental: AK159 SD 4<br>Single administration of AK159 dose level 4 | Drug: AK159<br>* transdermal administration of teriparatide acetate<br>|
| Active Comparator: MN-10-T SD<br>Single administration of teriparatide acetate | Drug: MN-10-T<br>* subcutaneous administration of teriparatide acetate<br>|
| Experimental: AK159 MD 1<br>Multiple administration of AK159 dose level 1 | Drug: AK159<br>* transdermal administration of teriparatide acetate<br>|
| Experimental: AK159 MD 2<br>Multiple administration of AK159 dose level 2 | Drug: AK159<br>* transdermal administration of teriparatide acetate<br>|
| Experimental: AK159 MD 3<br>Multiple administration of AK159 dose level 3 | Drug: AK159<br>* transdermal administration of teriparatide acetate<br>|
| Experimental: AK159 MD 4<br>Multiple administration of AK159 dose level 4 | Drug: AK159<br>* transdermal administration of teriparatide acetate<br>|
| Active Comparator: MN-10-T MD<br>Multiple administration of MN-10-T | Drug: MN-10-T<br>* subcutaneous administration of teriparatide acetate<br>|
| Placebo Comparator: Placebo MD<br>Multiple administration of placebo AK159 | Drug: Placebo<br>* Placebo AK159<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the plasma concentration versus time curve (AUC) of teriparatide |  | up to 6 hours after single and repeated administration | 
| Peak Plasma Concentration (Cmax) of teriparatide |  | up to 6 hours after single and repeated administration | 
| Number of subjects with adverse events and Incidence of adverse events |  | up to 7 weeks after the initial administration | 
| Change in bone turnover markers from baseline |  | up to 7 weeks after the initial administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual assessment of the application site |  | up to 7 weeks after the initial administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AK159, teriparatide acetate