Active Comparator Study of Generex Oral-lyn™ Spray and Injected Human Insulin

Study Overview
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Brief Summary
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To compare the efficacy of Generex Oral-lyn™ RapidMist™ System and standard regular human insulin therapy as measured by HbA1c, in type-1 diabetes mellitus subjects on BID NPH intermediate acting insulin therapy.

Detailed Description
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This is a 26 week open-label, randomized, multi-center, active comparator study to compare oral spray insulin (Generex Oral-lyn™) with regular human insulin therapy as measured by HbA1c, and number of hypoglycaemic episodes in type-1 diabetes mellitus subject. All subjects will be on BID NPH intermediate acting insulin therapy. If subject is using long acting insulin (Glargine, Detemir, etc.), he/she must be switched to NPH intermediate acting insulin. If on insulin analogue (Novolog, Lispro, Aspart, Aphidra, Glulisine, or any other analogue available in the subject's geographical area), the subject must be switched to regular human insulin 3 times a day.

Official Title
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A 26-Week, Open-Label, Randomized, Active Comparator Study of Generex Oral-lyn™ Spray and Injected Human Insulin In Subjects With Type-1 Diabetes Mellitus

Conditions
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Diabetes Mellitus

Intervention / Treatment
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* Drug: Generex Oral-lyn™
* Drug: Regular human insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be male or female between the ages 18 to 75 years Type 1 diabetes mellitus patients (according to ADA and/or WHO classification) who have >1 year history of type 1 DM and are currently managed with daily insulin injections totalling 0.3 to 0.8 IU/kg of body weight; Current physical examination, vital signs and ECG at screening that reveals no clinically significant abnormalities; Have a body mass index (BMI) <27; 8.5% (inclusively)<Have a glycosylated haemoglobulin HbA1c Willing and able to follow the American Diabetes Association diet guidelines for type 1 diabetes; be able to commit to perform home blood glucose monitoring and record values as well as hypoglycemic events Willing to give written informed consent prior to admission into the study. Exclusion Criteria: Have a significant active asthma or suspected abnormalities of buccal mucosa; cardiovascular, cerebrovascular, hepatic, renal, gastrointestinal, hematological, or auto-immune disease (other than auto-immune thyroid disease); history of athopy or drugs allergy Have evidence of unstable retinopathy (defined as pre-proliferative or proliferative retinopathy currently requiring photocoagulation therapy), nephropathy or neuropathy (gastroparesis or orthostatic hypotension); Have hypoglycemia unawareness; Have had more than one episode of severe hypoglycemia with seizure or coma or ketoacidosis within the past 12 months; Have a blood pressure in excess of 160/100 mmHg at the Screening visit; Have had any acute illness within the 2 weeks prior to screening; Have a history of drug or alcohol abuse that in the opinion of the Investigator would interfere with participation in the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Generex Oral-lyn™ spray in a split-dose fashion (half the dose immediately prior to the meal and half the dose immediately after the meal) + BID NPH insulin AM and PM as pre-randomization dose | Drug: Generex Oral-lyn™<br>* Generex Oral-lyn™ spray in a split-dose fashion (half the dose immediately prior to the meal and half the dose immediately after the meal) + BID NPH insulin AM and PM as pre-randomization dose<br>* Other names: buccal Insulin spray;|
| Active Comparator: 2<br>Regular human insulin 30 minutes before meals + BID NPH insulin AM and PM as pre-randomization dose. | Drug: Regular human insulin<br>* Regular human insulin 30 minutes before meals + BID NPH insulin AM and PM as pre-randomization dose.<br>* Other names: insulin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the efficacy of Generex Oral-lyn™ RapidMist™ System and standard regular human insulin therapy as measured by HbA1c, in type-1 diabetes mellitus subjects on BID NPH intermediate acting insulin therapy |  | change in HbA1c from the Day 0 (V3) to Day 180 (V9) of Treatment Phase. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety, tolerability, and satisfaction with Generex Oral-lyn™ therapy when administered by the RapidMist™ Diabetes Management System |  | 26 week |