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

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

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.

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: Generex Oral-lyn™; Drug: Regular human insulin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • 1 Hristo Smirnensky St, Bulgaria, 9010
    • University Multiprofile Hospital for Active Treatment at Varna
  • 11 Armeyska St., Bulgaria, 6003
    • Multiprofile Hospital for Active Treatment at Stara Zagora
  • 15A Vassil Aprilov Blvd, Bulgaria, 4002
    • University Multiprofile Hospital for Active Treatment at Plovdiv
  • 2 Nezavisimost St, Bulgaria, 7002
    • Multiprofile Hospital for Active Treatment at Ruse
  • 8A Georgi Kotchev St, Bulgaria, 5800
    • University Multiprofile Hospital for Active Treatment at Pleven
  • Sofia
    • 1 St. Georgi Sofiysky St, Sofia, Bulgaria, 1431
      • University Multiprofile Hospital for Active Treatment "Aleksandrovska"
• Canada
  • Alberta
    • #108 3947 50A Avenue, Alberta, Canada, T4N 6V7
      • The Bailey Clinic at Red Deer
    • #23, 4411-16th Avenue NW, Alberta, Canada, T3B 0M3
      • Calgary Metabolic Education & Research Centre at Calgary
    • 10230 142 St Nw # 25, Edmonton, Alberta, Canada, T5N 3Y6
      • West Edmonton Diabetes Centre
• Ecuador
  • Quito
    • Avenida La Coruña Nº 6337 y San Ignacio, Quito, Ecuador
      • Instituto de Endocrinologia IEMYR
• Poland
  • ul. Baczynskiego 17, Poland, 85 - 822
    • Bydgoszcz Diabetology and Endocrinology Center at Bydgoszcz
  • ul. Bialobrzeska 40A, Poland, 02 - 341
    • OSTEOMED Medical Center at Warszawa
  • ul. Kondratowicza 8, Poland, 03 - 242
    • Chair and Department of Internal Medicine and Diabetology, Voivodship Brodnowski Hospital at Warszawa
  • ul. Krolewiecka 146, Poland, 82 -300
    • Diabetology Clinic for Adults, NZOZ Elblag Diabetology Center
  • ul. Mazowiecka 56, Poland, 35-324
    • TeMeD - Clinical Trials at Rzeszow
  • ul. Nowa 30/32, Poland, 90-030
    • Provincial Centre of Diabetology and Metabolic Diseases, M.Pirogow Provincial Specialist Hospital at Lodz
  • ul. Opolska 11/3, Poland, 40-084
    • Silesia Osteoporosis Center at Katowice
  • ul. Wojska Polskiego 14, Poland, 34-400
    • TeMeD - Clinical Trials at Nowy Targ
  • ul. Zamenhofa 10/20, Poland, 15 - 435
    • NZOZ Specialist Centre of Internal Medicine and Diabetology Malgorzata Arciszewska at Bialystok
• Puerto Rico
  • Fajardo, Puerto Rico, 00738
    • Celis Aguilera 10B
  • San Juan, Puerto Rico, 364246
    • Puerto Medical Center
  • San Juan, Puerto Rico
    • Clinical Research, Puerto Rico
• Romania
  • 12 Vergului St Sector 2, Romania, 022441
    • "Nicolae Malaxa" Clinical Hospital, Department of Diabetes, Nutrition and Metabolic Diseases at Bucharest
  • 156 Iosif Bulbuca Av, Romania, 300736
    • Timisoara Emergency Clinical County Hospital, Clinic of Diabetes, Nutrition and Metabolic Diseases at Timisoara
  • 2-3 Eroii Revolutiei Square, Romania, 440055
    • Satu Mare County Hospital, Department of Diabetology and Nutrition Diseases at Satu Mare
  • 25 Constructorilor St, Bl. E5/64, Romania, 800371
    • Private Practice at Galati
  • 3-5 Clinicilor St, Romania, 400006
    • Cluj Emergency Clinical County Hospital, Department of Diabetes, Nutrition and Metabolic Diseases at Cluj-Napoca
  • 33 Republicii St, Romania, 410032
    • Oradea Clinical County Hospital, Department of Diabetes, Nutrition and Metabolic Diseases at Oradea
  • 5-7 Ion Movila St Sector 2, Romania, 020475
    • National Institute of Diabetes, Nutrition and Metabolic Diseases, 1st Clinical Department of Diabetes, Nutrition and Metabolic Diseases at Bucharest
  • 6/72 Independentei St, Romania, 430123
    • Cardiology Private Practice at Bala Mare
  • 92 Polona St, Bl 17 A+B, Sc. 1, Ap. 2, Romania, 010507
    • Private Practice Nicodiab SRL at Bucharest
• Russian Federation
  • 1 3rd -Transportnaya str., Omsk, Russian Federation, 644021
    • Municipal Medical Institution: City Hospital # 2, Municipal Diabetology and Rehabilitation Center
  • 1 Severny Pr., St.Petersburg, Russian Federation, 194354
    • St. Petersburg State Medical Institution: St. George Municipal Hospital
  • 1 Truda str., Izhevsk, Russian Federation, 426067
    • Municipal Medical Institution: Medical Unit "Izhmash", Municipal Endocrinology Center
  • 10 Siqueirosa str., St. Petersburg, Russian Federation, 194354
    • St. Petersburg State Medical Institution: Municipal Consulting and Diagnostic Center #1, St. Petersburg Territorial Diabetology Center
  • 11 Dmitriya Ulyanova str., Moscow, Russian Federation, 117036
    • Federal State Institution: Endocrinology Research Center under the Federal Agency for High-Tech Medical Care, Department of Therapeutic and Surgical Methods for Treatment of Diabetic Foot
  • 11 Dmitriya Ulyanova str., Moscow, Russian Federation, 117036
    • Federal State Institution: Endocrinology Research Center under the Federal Agency for High-Tech Medical Care, Department of Training and Psychosocial Rehabilitation of Patients with Diabetes Mellitus
  • 14 Vavilovykh str., St. Petersburg, Russian Federation, 195257
    • St. Petersburg State Medical Institution: Municipal Hospital of St. Elizabeth
  • 190 Rodionova str., Nizhny Novgorod, Russian Federation, 603126
    • State Medical Institution: Nizhny Novgorod Regional Clinical Hospital n.a. N.A. Semashko
  • 2 "b" Salyama Adilya str., Moscow, Russian Federation, 123423
    • Medical Institution Municipal Clinical Hospital #67
  • 22 Oktyabrsky Pr., Kemerovo, Russian Federation, 650066
    • State Medical Institution: Kemerovo Regional Clinical Hospital
  • 292 Lomonosova pr., Arkhangelsk, Russian Federation, 163045
    • State Medical Institution: Arkhangelsk Regional Clinical Hospital
  • 3 Pirogova str., Petrozavodsk, ,, Russian Federation, 185019
    • State Medical Institution: Republican Hospital
  • 33/35 Kosmonavtov Pr., St. Petersburg, Russian Federation, 196211
    • St. Petersburg State Medical Institution:Municipal Outpatient Clinic #51
  • 4 Shkuleva str., Moscow, Russian Federation, 109263
    • Moscow State Medical Institution Municipal Clinical Hospital #68
  • 4 Solidarnosti Pr., St. Petersburg, Russian Federation, 193312
    • St. Petersburg State Medical Institution: City Aleksandrovskaya Hospital
  • 4/2 Lebedeva str., St.Petersburg, Russian Federation, 194044
    • Federal State Medical Institution: All-Russia Center for Urgent Care and Radiation Medicine n.a. A.M. Nikiforov under the Russian Emergency Control Ministry
  • 5 Uchebny Per., St. Petersburg, Russian Federation, 194354
    • St. Petersburg State Medical Institution: Municipal Multifield Hospital #2
  • 54 Odesskaya str., Tyumen, Russian Federation, 625023
    • State Higher Educational Institution: Tyumen State Medical Academy under the Federal Agency for Healthcare and Social Development, Multifield Clinic
  • 56 Sovetskoi Armii str., Samara, Russian Federation, 443067
    • "Diabetes" Center Company Limited
  • 6 Kuratova str., 167981, Russian Federation, Syktyvkar
    • State Medical Institution: Consulting and Diagnostic Center of Komi Republic, Diabetology Center
  • 6 Pavlova str., Building 4, Murmansk, Russian Federation, 183047
    • State Medical Institution: Murmansk Regional Consulting and Diagnostic Center
  • 6 Zalesskogo str., Novosibirsk, Russian Federation, 630047
    • Municipal Medical Institution: Municipal Clinical Hospital #1, Municipal Diabetology Center
  • 6/8 L. Tolstogo str., St. Petersburg, Russian Federation, 197022
    • State Higher Educational Institution: St. Petersburg State Medical University n.a. I.P. Pavlov under the Federal Agency for Healthcare and Social Development
  • 61/2 Shchepkina str., Moscow, Russian Federation, 129110
    • State Institution: Moscow Regional Research Clinical Institute n.a. M.F.Vladimirsky
  • 7 Kluchevskaya str., Ekaterinburg, Russian Federation, 620219
    • State Higher Educational Institution: Ural State Medical Academy under the Federal Agency for Healthcare and Social Development; Family Medicine Clinic
  • 70 Vorovskogo str., Medgorodok, Chelyabinsk, Russian Federation, 454076
    • State Medical Healthcare Institution: Chelyabinsk Regional Clinical Hospital
  • 9 Artema str., Stavropol, Russian Federation, 355045
    • State Medical Institution:Territorial Endocrinology Center, Territorial Diabetology Center
• Ukraine
  • 1, Ostrozskoho St., Lviv, Ukraine, 79010
    • Regional Endocrinology Center, Diabetology Department at Lviv
  • 121, Kharkovskoe Shosse, Kiev, Ukraine, 02175
    • Ukrainian Research and Development Center for Endocrine Surgery and Endocrine Organ and Tissue Transplantation under the Ministry of Health of Ukraine, General Endocrine Pathology Department at Kiev
  • 23, Shevchenko St., Ukraine, 36024
    • M.V. Sklifosovskyi Regional Clinical Hospital, Endocrinology Department at Poltava
  • 29, Vorontsova St., Ukraine, 49023
    • City Clinical Hospital #9, Endocrinology Department at Dnipropetrovsk
  • 69 Kievskaya St., Ukraine, 95017
    • M.O. Semashko Republican Clinical Hospital, Endocrinology Department at Simferopol
  • 69, Vyshgorodskaya St., Kiev, Ukraine, 04114
    • V.P. Komisarenko Institute for Endocrinology and Metabolism under the Ukrainian Academy of Medical Sciences, Clinical Diabetology Department at Kiev
  • 69, Vyshgorodskaya St., Kiev, Ukraine, 04114
    • V.P. Komisarenko Institute for Endocrinology and Metabolism under the Ukrainian Academy of Medical Sciences, General Endocrine Pathology Department at Kiev
  • Pomerky 27, Kharkov, Ukraine, 61070
    • V.Ya. Danylevskyi Institute for Endocrine Pathology under the Ukrainian Academy of Medical Sciences, Clinical Endocrinology Department at Kharkov
• United States
  • California
    • 2001 Santa Monica Blvd Suite 390W, California, United States, 90404
      • Coastal Biomedical Research Inc. at Santa Monica
  • Florida
    • 1150 N. 35th Ave Suite 590, Florida, United States, 33021
      • The Center for Diabetes & Endocrine Care at Hollywood
  • Indiana
    • 7400 North Shadeland Ave, Indiana, United States
      • Physicians Research Group at Indianapolis
  • Maryland
    • 6535 North Charles Street Suite 400N, Maryland, United States, 21204
      • MODEL Clinical Research at Baltimore
  • Michigan
    • 43494 Woodward Ave Suite 208, Michigan, United States, 48302
      • Grunberger Diabetes Institute at Bloomfield Hills
  • New York
    • 317 East 17th Street Room 7F05 8th Floor, New York, United States, 10003
      • Beth Israel Medical Center, Geral J. Friedman Diabetes Institute at New York
  • Texas
    • 501 Rita Lane Suite 113, Texas, United States, 76014
      • Multiple Health Research, LLC. at Arlington
    • 5323 Harry Hines Blvd, Texas, United States, 75390-8858
      • University of Texas Southwestern Medical Center at Dallas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; 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™; 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; Other Names: buccal Insulin spray
Active Comparator: 2; Regular human insulin 30 minutes before meals + BID NPH insulin AM and PM as pre-randomization dose.	Drug: Regular human insulin; Regular human insulin 30 minutes before meals + BID NPH insulin AM and PM as pre-randomization dose.; Other Names: insulin

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Generex Biotechnology Corp.
• Collaborators: Hoffmann-La Roche; Nextrials, Inc.; eResearch Technology, Inc.; OSMOS Clinical Research, Inc; PSI Pharma Support Intl; ACM Pivotal Global Central Laboratory
• Investigators: Study Chair: Gerald Bernstein,, MD, Generex Biotechnology Corp.; Study Director: Jaime Davidson, MD, Generex Biotechnology Corp.; Principal Investigator: Philip Raskin, MD, University of Texas, Southwestern Medical Center at Dallas

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Anticipated): August 1, 2011
• Study Completion (Anticipated): September 1, 2011

Study Registration Dates

• First Submitted: April 24, 2008
• First Submitted That Met QC Criteria: April 28, 2008
• First Posted (Estimate): April 29, 2008

Study Record Updates

• Last Update Posted (Estimate): June 8, 2011
• Last Update Submitted That Met QC Criteria: June 6, 2011
• Last Verified: June 1, 2011

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: GEN-084-OL