Comparative Bioavailability of Betamethasone Oral Solution Metered Spray (GTX-102) in Healthy Subjects

Study Overview
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Brief Summary
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A Randomized, Open-label, Crossover Study to Evaluate the Comparative Bioavailability, Pharmacokinetics, and Safety of GTX-102 Administered as an Oral Spray Compared to Intramuscular Injection - betamethasone and an Oral Solution of Betamethasone in Healthy Subjects. Four groups of subjects will receive 2 treatments each and randomized in 2-way crossover.

Official Title
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Crossover Study to Evaluate the Comparative Bioavailability, Pharmacokinetics, and Safety of GTX-102 Administered as an Oral Spray Compared to Intramuscular Injection and an Oral Solution of Betamethasone in Healthy Subjects

Conditions
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Ataxia Telangiectasia

Intervention / Treatment
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* Drug: GTX-102 medium dose fast Period 1 and Period 2
* Drug: GTX-102 medium dose slow Period 1 and Period 2
* Drug: GTX-102 high dose fast Period 1 and Period 2
* Drug: GTX-102 low dose fast Period 1 and Period 2
* Drug: Betamethasone solution as intramuscular injection Period 1 and Period 2
* Drug: Betamethasone Oral Solution Period 1 and Period 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female subjects between the ages of 18 and 55 years, inclusive. Willing and able to provide written informed consent prior to participating in the study. Able to communicate clearly with the Investigator and staff; able to read, complete questionnaires, and understand study procedures. Able to complete all screening period evaluations, and stay in the clinic testing facility for up to 2 consecutive days on 2 separate occasions. Body mass index (BMI) between 18 and 32 kg/m2, inclusive, and body weight between 40 and 120 kg, inclusive. Exclusion Criteria: Has a history of or current clinically significant medical illness including (but not limited to) pulmonary, cardiovascular, coagulation disorders, lipid abnormalities, gastrointestinal, immunologic, endocrine (stable thyroid hormone replacement therapy is not excluded), neurologic, psychiatric, or thromboembolic disease, metabolic disturbances, or any other current physical condition that the Investigator considers should exclude the participant, or that could interfere with the interpretation of the study results. Has current or recent (within 6 months) history of gastrointestinal disease, or any surgical or medical condition such as Crohn's disease or liver disease, that could potentially alter the absorption, metabolism, or excretion of the study drug. Has any clinically significant medical condition, physical examination finding, vital signs, ECG abnormality (at screening), or clinically significant abnormal value for hematology, serology, clinical chemistry, or urinalysis at screening or at admission to the study center, as deemed appropriate by the Investigator

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 GTX-102 medium dose fast or slow in Period 1 and Period 2<br>GTX-102 Betamethasone oral spray medium dose (0.05 mg/kg) administered fast or slow over two periods | Drug: GTX-102 medium dose fast Period 1 and Period 2<br>* GTX-102 Betamethasone oral spray medium dose (0.05 mg/kg) administered in Period 1 and Period 2 fast<br>Drug: GTX-102 medium dose slow Period 1 and Period 2<br>* GTX-102 Betamethasone oral spray medium dose (0.05 mg/kg) administered in Period 1 and Period 2 slow<br>|
| Experimental: Group 2a GTX-102 high dose fast in Period 1 and Period 2<br>GTX-102 Betamethasone oral spray high dose (0.1 mg/kg) administered fast over two periods Note: Note under US IND | Drug: GTX-102 high dose fast Period 1 and Period 2<br>* GTX-102 Betamethasone oral spray high dose (0.1 mg/kg) administered in Period 1 and Period 2 fast<br>|
| Active Comparator: Group 2b Oral comparator in Period 1 and Period 2<br>0.1 mg/kg betamethasone solution oral drops solution over two periods Note: Not under US IND | Drug: Betamethasone Oral Solution Period 1 and Period 2<br>* Comparator product 0.1 mg/kg betamethasone oral drops solution<br>|
| Experimental: Group 3 GTX-102 high dose fast or low dose fast in Period 1 and Period 2<br>GTX-102 Betamethasone oral spray high dose (0.1 mg/kg) or GTX-102 Betamethasone oral spray low dose (0.025 mg/kg) administered fast over two periods | Drug: GTX-102 high dose fast Period 1 and Period 2<br>* GTX-102 Betamethasone oral spray high dose (0.1 mg/kg) administered in Period 1 and Period 2 fast<br>Drug: GTX-102 low dose fast Period 1 and Period 2<br>* GTX-102 Betamethasone oral spray high dose (0.025 mg/kg) administered in Period 1 and Period 2 fast<br>|
| Experimental: Group 4a GTX-102 high dose fast in Period 1 and Period 2<br>GTX-102 Betamethasone oral spray high dose (0.1 mg/kg) administered fast over two periods | Drug: GTX-102 high dose fast Period 1 and Period 2<br>* GTX-102 Betamethasone oral spray high dose (0.1 mg/kg) administered in Period 1 and Period 2 fast<br>|
| Active Comparator: Group 4b betamethasone intramuscular in Period 1 and Period 2<br>0.1 mg/kg betamethasone solution as intramuscular injection administered over two periods | Drug: Betamethasone solution as intramuscular injection Period 1 and Period 2<br>* reference product 0.1 mg/kg betamethasone solution as an intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC from 0 to 72 hours post-dose | Area under the curve | Up to 72 hours post-dose | 
| AUC | Area under the curve | Up to infinity | 
| Cmax from 0 to 72 hours post-dose | Maximum concentration | Up to 72 hours post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events from Day 1 to Day 45 | Adverse events | Day 1 to Day 45 | 
| Relative bioavailability of GTX-102 oral spray versus betamethasone oral solution and betamethasone intramuscular injection | Area under the curve (AUC0-t) | Up to 72 hours post-dose | 
| Relative bioavailability of GTX-102 oral spray versus betamethasone oral solution and betamethasone intramuscular injection | Area under the curve (AUC0-inf) | Up to infinity |