Clinical 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 Part 1 and Part 2. <Part 1> Part 1 will be conducted according to a single-centre, randomized, single-dose, 3-period, 5-treatment alternating crossover design in two groups of healthy post-menopausal women The pharmacokinetics, safety, and tolerability of a single dose of AK159 (4 levels) will be investigated versus teriparatide acetate for injection as a control. <Part 2> Part 2 will be conducted according to a multiple-centre, randomized, double-blind, placebo-controlled, repeated dose parallel design of healthy post-menopausal women The pharmacokinetics, safety, and tolerability of AK159 (4 levels) for 8 weeks will be investigated versus teriparatide acetate for injection and placebo as controls. Pharmacokinetics, safety, and tolerability following long-term application will also be investigated.

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; and 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 Systolic blood pressure < 90 mmHg QTc exceeds 470 msec in a 12-lead electrocardiography 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: Quadruple


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 MN-10-T | 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>* Multiple administration of 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 Participants with Adverse Events, Vital signs, ECG parameters, and 24-hour ECG holter recording (for Part 2 of the study). |  | up to 24 hours after single and repeated administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in bone turnover markers within 24 hrs at each administration |  |  | 
| Residual teriparatide in the patch after application |  |  | 

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