SCREENING Visit Date: DEMOGRAPHICS / / [YYYY/MM/DD] Consent Signed Date and time / / [YYYY/MM/DD] : Has written assent been obtained? If no, why not? YES NO Gender: Male Female Birthdate: Permission given to store samples? / / [ YYYY/MM/DD] YES NO PHYSICAL ATTRIBUTES Height. cm t done Weight. kg t done Waist circumference First attempt Second attempt Average of 2 attempts. cm. cm. cm t done BMI. kg/m 2 t done VITAL SIGNS Heart Rate / Min t done Resp. Rate /Min t done Temperature. o C t done Sitting BP / t done Version: 01-Jun-2014 Completed by (initials): Page 1 of 28
SCREENING PHYSICAL EXAMINATION Body System Normal? Comment if not normal Head, Eyes, Ears, Nose, and Throat (HEENT) Respiratory Abdominal/ Gastrointestinal (GI) Pulmonary Cardiovascular Endocrine Musculoskeletal Neurologic/ Central Nervous System (CNS) Psychiatric Immunologic/ Allergy Gynecologic/ Urologic Other, specify: Version: 01-Jun-2014 Completed by (initials): Page 2 of 28
SCREENING RELEVANT HISTORY Has the subject ever been admitted to the hospital? Has the subject been diagnosed with a chronic disease? Has the subject been diagnosed with depression? Does the subject currently suffer from any allergies? Has the subject ever suffered from (or is currently suffering from) any other significant condition other than the study condition? If yes then please document on the medical history form. If yes then please document on the medical history form. If yes then please document on the medical history form. If yes then please document on the medical history form. If yes then please document on the medical history form. Any family history of Type 1 Diabetes? (1) Any family history of Type 1 Diabetes? (2) If yes, who: If yes, who: Any family history of Type 2 Diabetes? If yes, who: Any family history of Gestational Diabetes? Subject s Education Does the subject have a job? Some high school High school graduate/ged Some post-secondary school after graduation College, trade, technical, vocation or business diploma or certificate University Graduate Some graduate school Graduate degree If yes, who: Other: If yes, number of hours a week: Version: 01-Jun-2014 Completed by (initials): Page 3 of 28
SCREENING Any participation in any sports teams? Any other recreational exercise Does the subject smoke? Does the subject drink alcoholic beverages? Does the subject use recreational drugs? Are the subject s vaccinations up to date? Is the subject sexually active? If yes, number of hours a week: If yes, number of hours a week: If yes, number of cigarettes a week: If yes, number of beverages a week: If yes, number of times using a week: PREGNANCY TEST Is the subject female and of childbearing potential? Yes If male then answer no. If yes then perform a pregnancy test and complete the questions below. Date of test / / [YYYY/MM/DD] Result Negative Positive Version: 01-Jun-2014 Completed by (initials): Page 4 of 28
SCREENING MEDICAL HISTORY Does the participant/subject have a history of any medical problems/conditions? Yes If yes then document below. Use the following Body System codes: 1. Constitutional symptoms (e.g., fever, weight loss) 2. Eyes 3. Ears, Nose, Mouth, Throat 4. Cardiovascular Body System Code Medical History Term (One per line) 5. Respiratory 6. Gastrointestinal 7. Genitourinary 8. Musculoskeletal 9. Integumentary (skin and/or breast) Start Date [YYYY/MM/DD] 10. Neurological 11. Psychiatric 12. Endocrine 13. Hematologic/Lymphatic 14. Allergic/Immunologic Ongoing End Date [YYYY/MM/DD] Yes Yes Yes Yes Yes Yes Yes Version: 01-Jun-2014 Completed by (initials): Page 5 of 28
SCREENING CURRENT MEDICATIONS Did the subject take any medications within 30 days of study start? Yes Is the subject currently taking any medications? Yes If yes to either of these questions then please complete enter details on the Concomitant Medications form at the back of this CRF. INCLUSION CRITERIA Subjects must satisfy all of the following criteria 1. 18 years of age or older Yes 2. Signed informed consent Yes 3. Sexually active subjects willing to use acceptable method of contraception while participating in study 4. Male, or female and of child bearing potential with a negative pregnancy test at screening. Yes Yes 5. Willing and able to comply with all study procedures Yes EXCLUSION CRITERIA Subjects must have NONE of the following criteria 1. Female and breastfeeding at screening or planning on becoming pregnant at any time during the study. 2. Use of any investigational product or investigational medical device within 30 days prior to screening Yes Yes 3. Exclusion criteria 3 Yes 4. Exclusion criteria 4 Yes 5. Exclusion criteria 5 Yes Version: 01-Jun-2014 Completed by (initials): Page 6 of 28
SCREENING ELIGIBILITY Does the subject meet the conditions for enrollment into the study? Yes If the subject is eligible perform the randomization and write their treatment code below. Treatment Code NOTES AUTHORIZATION Principal Investigator Signature // Date [YYYY/MM/DD] Version: 01-Jun-2014 Completed by (initials): Page 7 of 28
BASELINE Visit Date: VITAL SIGNS / / [YYYY/MM/DD] Heart Rate / Min t done Resp. Rate /Min t done Temperature. o C t done Sitting BP / t done PHYSICAL EXAMINATION Body System Normal? Comment if not normal Head, Eyes, Ears, Nose, and Throat (HEENT) Respiratory Abdominal/ Gastrointestinal (GI) Pulmonary Cardiovascular Endocrine Musculoskeletal Neurologic/ Central Nervous System (CNS) Psychiatric Version: 01-Jun-2014 Completed by (initials): Page 8 of 28
BASELINE Immunologic/ Allergy Gynecologic/ Urologic Other, specify: BLOOD CHEMISTRY Date of test Is participant fasting? If fasting, time last eaten. t done / / [YYYY/MM/DD] Yes : (24 hour clock) Na K Cl TCO2 Ca Mg PO4 PTH Glucose Urea Creatinine Vitamin D Albumin T Protein Are any of these results clinically significant? mmol/l t Done. mmol/l t Done mmol/l t Done mmol/l t Done. mmol/l t Done. mmol/l t Done. mmol/l t Done ng/l t Done. mmol/l t Done. mmol/l t Done umol/l t Done nmol/l t Done g/l t Done g/l t Done Yes Version: 01-Jun-2014 Completed by (initials): Page 9 of 28
BASELINE If yes then please comment below. Comments: ADVERSE EVENTS / MEDICATIONS / DEVIATIONS Have there been any changes to the subject s medications since the last visit? Have there been any adverse events related to the study drug since the last study visit Has there been any protocol deviations reported related to this study visit? YES NO If yes, please complete an entry in the Concomitant Medications Log. YES NO If YES, please complete Adverse Event Log. YES NO If YES, please complete Protocol Deviation Log. MEDICATION ACCOUNTABILITY Treatment Code (Should match the code allocated at screening) Date distributed Bottle ID # Number of pills distributed / / [YYYY/MM/DD] Version: 01-Jun-2014 Completed by (initials): Page 10 of 28
BASELINE NOTES AUTHORIZATION Principal Investigator Signature // Date [YYYY/MM/DD] Version: 01-Jun-2014 Completed by (initials): Page 11 of 28
FOLLOW UP 1 Visit Date: VITAL SIGNS / / [YYYY/MM/DD] Heart Rate / Min t done Resp. Rate /Min t done Temperature. o C t done Sitting BP / t done PHYSICAL EXAMINATION Body System Normal? Comment if not normal Head, Eyes, Ears, Nose, and Throat (HEENT) Respiratory Abdominal/ Gastrointestinal (GI) Pulmonary Cardiovascular Endocrine Musculoskeletal Neurologic/ Central Nervous System (CNS) Psychiatric Version: 01-Jun-2014 Completed by (initials): Page 12 of 28
FOLLOW UP 1 Immunologic/ Allergy Gynecologic/ Urologic Other, specify: BLOOD CHEMISTRY Date of test Is participant fasting? If fasting, time last eaten. t done / / [YYYY/MM/DD] Yes : (24 hour clock) Na K Cl TCO2 Ca Mg PO4 PTH Glucose Urea Creatinine Vitamin D Albumin T Protein Are any of these results clinically significant? mmol/l t Done. mmol/l t Done mmol/l t Done mmol/l t Done. mmol/l t Done. mmol/l t Done. mmol/l t Done ng/l t Done. mmol/l t Done. mmol/l t Done umol/l t Done nmol/l t Done g/l t Done g/l t Done Yes Version: 01-Jun-2014 Completed by (initials): Page 13 of 28
FOLLOW UP 1 If yes then please comment below. Comments: ADVERSE EVENTS / MEDICATIONS / DEVIATIONS Have there been any changes to the subject s medications since the last visit? Have there been any adverse events related to the study drug since the last study visit Has there been any protocol deviations reported related to this study visit? YES NO If yes, please complete an entry in the Concomitant Medications Log. YES NO If YES, please complete Adverse Event Log. YES NO If YES, please complete Protocol Deviation Log. Version: 01-Jun-2014 Completed by (initials): Page 14 of 28
FOLLOW UP 1 MEDICATION ACCOUNTABILITY Did the subject return the unused medication? If yes, how many pills were returned? Please account for any unused medication: YES NO Was a new bottle of medication given to the study subject? Treatment Code YES NO If yes then please complete the details below. (Should match the code allocated at screening) Date distributed Bottle ID # Number of pills distributed / / [YYYY/MM/DD] NOTES AUTHORIZATION Principal Investigator Signature // Date [YYYY/MM/DD] Version: 01-Jun-2014 Completed by (initials): Page 15 of 28
FINAL FOLLOW UP 1 Visit Date: VITAL SIGNS / / [YYYY/MM/DD] Heart Rate / Min t done Resp. Rate /Min t done Temperature. o C t done Sitting BP / t done PHYSICAL EXAMINATION Body System Normal? Comment if not normal Head, Eyes, Ears, Nose, and Throat (HEENT) Respiratory Abdominal/ Gastrointestinal (GI) Pulmonary Cardiovascular Endocrine Musculoskeletal Neurologic/ Central Nervous System (CNS) Psychiatric Version: 01-Jun-2014 Completed by (initials): Page 16 of 28
FINAL FOLLOW UP 1 Immunologic/ Allergy Gynecologic/ Urologic Other, specify: BLOOD CHEMISTRY Date of test Is participant fasting? If fasting, time last eaten. t done / / [YYYY/MM/DD] Yes : (24 hour clock) Na K Cl TCO2 Ca Mg PO4 PTH Glucose Urea Creatinine Vitamin D Albumin T Protein Are any of these results clinically significant? mmol/l t Done. mmol/l t Done mmol/l t Done mmol/l t Done. mmol/l t Done. mmol/l t Done. mmol/l t Done ng/l t Done. mmol/l t Done. mmol/l t Done umol/l t Done nmol/l t Done g/l t Done g/l t Done Yes Version: 01-Jun-2014 Completed by (initials): Page 17 of 28
FINAL FOLLOW UP 1 If yes then please comment below. Comments: ADVERSE EVENTS / MEDICATIONS / DEVIATIONS Have there been any changes to the subject s medications since the last visit? Have there been any adverse events related to the study drug since the last study visit Has there been any protocol deviations reported related to this study visit? YES NO If yes, please complete an entry in the Concomitant Medications Log. YES NO If YES, please complete Adverse Event Log. YES NO If YES, please complete Protocol Deviation Log. MEDICATION ACCOUNTABILITY Did the subject return the unused medication? If yes, how many pills were returned? Please account for any unused medication: YES NO Version: 01-Jun-2014 Completed by (initials): Page 18 of 28
FINAL FOLLOW UP 1 NOTES AUTHORIZATION Principal Investigator Signature // Date [YYYY/MM/DD] Version: 01-Jun-2014 Completed by (initials): Page 19 of 28
STUDY COMPLETION Did the subject complete the study? If not, why not? Yes Lost to follow-up Withdrew consent Other (please comment) Adverse event n-compliance Comments: Date of discontinuation or completion. / / [YYYY/MM/DD] AUTHORIZATION Principal Investigator Signature // Date [YYYY/MM/DD] Version: 01-Jun-2014 Completed by (initials): Page 20 of 28
CONCOMITANT MEDICATIONS INSTRUCTIONS The Concomitant Medications form should be filled out at the screening visit and every study visit/time point thereafter. It may be helpful to ask study participants/subjects or their caregivers to bring prescription and over-the-counter medications to follow-up visits so that the medications can be more easily and accurately recorded on the CRF. Medication Name Record the verbatim name (generic or trade name) of the medication the participant/subject reports taking. See the data dictionary for additional information on coding the medication name using RXNorm. Indication Record the reason the participant/subject gives for taking the medication. If given for an AE, enter exact term from Adverse Event CRF. Dose Record the strength of the medication the participant/subject is taking. Dose Units - Record the units of the medication the participant/subject is taking. Frequency - Record how often the medication is being taken. Route Record the route of administration. Acceptable responses for Route are shown below the medication table. Start Date Record the date the participant/subject started taking the medication. The date should be recorded to the level of granularity known (e.g., year, year and month, complete date) and in the specified format to the study database. Start Date can be used to distinguish between prior medications and concomitant medications. Ongoing? Choose one. Answer YES if the participant/subject is still taking the medication or NO if the participant/subject has stopped taking the medication. End Date Record the date the participant/subject stopped taking the medication. The date/time should be recorded to the level of granularity known and in the specified format. End Date should be recorded if Ongoing is answered NO. Conversely, End Date should remain blank if Ongoing is answered YES. Version: 01-Jun-2014 Completed by (initials): Page 21 of 28
CONCOMITANT MEDICATIONS CONCOMITANT MEDICATIONS Medication Name Indication Dose Dose Unit Frequency Route Start Date [YYYY/MM/DD] Ongoing End Date [YYYY/MM/DD] Yes Yes Yes Yes Yes Yes Yes Version: 01-Jun-2014 Completed by (initials): Page 22 of 28
ADVERSE EVENTS ADVERSE EVENTS Adverse events (AEs) document medical events that occur to a participant/subject once enrolled in a study. AEs are the construct through which the safety of an intervention is recorded and assessed during a study. RECORDING ADVERSE EVENTS All AEs, both serious and non-serious, regardless of relationship to the study intervention, should be recorded on the AE case report form (CRF). AE data should be collected from the time the informed consent form is signed through the duration of the clinical investigation. Standard medical terminology should be used when recording AEs. SERIOUS ADVERSE EVENTS A serious adverse event is (SAE) defined as any untoward medical occurrence that at any dose results in one of the following outcomes: Death; A life-threatening adverse drug experience; Results in inpatient hospitalization or prolongation of existing hospitalization; A persistent or significant disability/incapacity; If an event is documented as serious, then a separate SAE Report form must completed. Because the data collected for an SAE are descriptive and beyond the scope of a study, the SAE information is usually kept in a separate file. SPECIFIC INSTRUCTIONS AE Description Any untoward medical occurrence in a study participant/subject that does not necessarily have a causal relationship with the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study intervention or study procedure, whether or not related to the study intervention or procedure. Each AE should be listed on a separate line. Any worsening of a baseline condition or reoccurrence of a baseline condition that had previously ended for a time should be listed as an AE. Events, such as nausea and vomiting are considered two events, and therefore should be listed on separate lines. A participant/subject may experience an unexpected AE. An unexpected adverse reaction has a nature or severity of which is not consistent with the study intervention description (e.g. Investigator's Brochure for an unapproved investigational product or package insert/summary of product characteristics for an approved product). The unexpected AE must be reported, whether related to the study intervention or not, with as much detail as is available Start Date Version: 01-Jun-2014 Completed by (initials): Page 23 of 28
ADVERSE EVENTS Record the date the adverse event started. The date should be recorded to the level of granularity known (e.g., year, year and month, complete date) and in the specified format. If a previously recorded AE worsens, a new record should be created with a new start date. There should be no AE start date prior to the date of the informed consent. Any AE that started prior to the informed consent date belongs instead in the medical history. If an item recorded on the medical history worsens during the study, the date of the worsening is entered as an AE with the start date as the date the condition worsened. End Date Record the date the adverse event stopped or worsened. The date should be recorded to the level of granularity known (e.g., year, year and month, complete date) and in the specified format. If an AE worsens, record an end date and create a new AE record with a new start date and severity. Severity Choose the one severity that best describes the investigator s assessment of the intensity of the AE. Severe events interrupt the participant s/subject s normal daily activities and generally require systemic drug therapy or other treatment; they are usually incapacitating. Consequently, a change in severity may constitute a new reportable AE. Severity is not synonymous with seriousness. A severe rash is not likely to be an SAE. Likewise, a severe headache is not necessarily an SAE. However, mild chest pain may result in a day s hospitalization and thus is an SAE. Relatedness Choose one. Record the investigator s assessment of the degree of relatedness of the AE to the study intervention.. Action Taken with Study Intervention Choose one. Other Action Taken Choose one. If treatment was required, then the corresponding treatment needs to be recorded on the Concomitant Medications CRF. Version: 01-Jun-2014 Completed by (initials): Page 24 of 28
ADVERSE EVENTS Outcome Choose one. The outcome of an AE may not be captured at the visit during which it was first reported, but must be captured to provide a complete picture of the event. Entering the outcome of an AE may be deferred until the AE is resolved, or the participant/subject completes the study. For AEs that have not resolved at the time of a study visit, the outcome should be marked as unresolved on the AE case report form. Serious Choose either Yes or No. This question should only be answered YES if the outcome of the AE results in at least one of the following: death; a life-threatening adverse drug experience; results in inpatient hospitalization or prolongation of existing hospitalization; a persistent or significant disability/incapacity; or a congenital anomaly/birth defect. If an AE is serious, this provides a trigger that additional information must be provided by the site investigator. The site investigator then completes a Serious Adverse Event (SAE) form. Additionally, the site institution and/or IRB may also have an SAE form and procedures for reporting SAEs. Version: 01-Jun-2014 Completed by (initials): Page 25 of 28
ADVERSE EVENTS Adverse Event Start Date [YYYY/MM/DD] Severity Relatedness Action Taken with study intervention Other Action Taken Outcome Serious? End Date [YYYY/MM/DD] 1. Mild Unrelated ne ne Recovered/Resolved Yes* Moderate Severe Life-threatening or Disabling Fatal/Death Unlikely Probable Possible Definite Study Intervention Interrupted Study Intervention Discontinued Study Intervention Modified n-study Treatment Required Recovered/Resolved With Sequelae Recovering / Resolving Unresolved / Not Recovered Fatal Unknown 2. Mild Unrelated ne ne Recovered/Resolved Yes* Moderate Severe Life-threatening or Disabling Fatal/Death Unlikely Probable Possible Definite Study Intervention Interrupted Study Intervention Discontinued Study Intervention Modified n-study Treatment Required Recovered/Resolved With Sequelae Recovering / Resolving Unresolved / Not Recovered Fatal Unknown 3. Mild Unrelated ne ne Recovered/Resolved Yes* Moderate Severe Life-threatening or Disabling Fatal/Death Unlikely Probable Possible Definite Study Intervention Interrupted Study Intervention Discontinued Study Intervention Modified n-study Treatment Required Recovered/Resolved With Sequelae Recovering / Resolving Unresolved / Not Recovered Fatal Unknown * Yes should be answered when the adverse event results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. Principal Investigator Signature // Date [YYYY/MM/DD] Version: 01-Jun-2014 Completed by (initials): Page 26 of 28
PROTOCOL DEVIATIONS *DEVIATION CATEGORIES: A. Safety B. Informed Consent C. Eligibility D. Protocol implementation E. Other, specify in log **DEVIATION CODES: Numbers listed by the sample protocol deviations Safety (Category A) 1. Not reporting an SAE within 24 hours 2. Laboratory tests not done 3. AE/SAE is not reported to IRB 4. Other, specify in log Informed Consent (Category B) 5. Failure to obtain informed consent 6. Consent form used was not current IRB-approved version 7. Consent form does not include updates or information required by IRB 8. Consent form missing 9. Consent form not signed and dated by participant 10. Consent form does not contain all required signatures 11. Other, specify in log Eligibility (Category C) 12. Participant did not meet eligibility criterion 13. Randomization of an ineligible participant 14. Participant randomized prior to completing Baseline Assessment, etc. 15. Randomization and/or treatment of participant prior to IRB approval of protocol 16. Other, specify in log Protocol implementation (Category D) 17. Failure to keep IRB approval up to date 18. Participant receives wrong treatment 19. Participant seen outside visit window 20. Use of unallowable concomitant treatments 21. Prescribed dosing outside protocol guidelines 22. Missed assessment 23. Missed visit 24. Other, specify in log Version: 01-Jun-2014 Completed by (initials): Page 27 of 28
PROTOCOL DEVIATIONS Description of Protocol Deviation: Deviation Category* Deviation Code** Date Deviation Occurred: (yyyy/mm/dd) Date IRB Notified (if applicable): 1) 2) 3) 4) 5) Version: 01-Jun-2014 Completed by (initials): Page 28 of 28