Clinical trial • Phase IV • Endocrinology

Dapagliflozin propanediol for Type 2 diabetes mellitus

Phase IV trial of Dapagliflozin propanediol for Type 2 diabetes mellitus.

Overview

Trial Therapeutic Area
Endocrinology
Trial Disease
Type 2 diabetes mellitus
Trial Stage
Phase IV
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
20-08-2024
First CTIS Authorization Date
30-08-2024

Trial design

Randomised, dapagliflozin (test): active substance dapagliflozin propanediol, oral, max daily dose 10 mg (product entry maxdailydoseamount 10 mg). metformin (comparator): metformin, oral, max daily dose 3000 mg (product entry maxdailydoseamount 3000 mg). detailed dosing schedules not specified in the ctis data.-controlled Phase IV trial in Sweden.

Randomised
Yes
Comparator
DAPAGLIFLOZIN (test): active substance dapagliflozin propanediol, oral, max daily dose 10 mg (product entry maxDailyDoseAmount 10 mg). METFORMIN (comparator): metformin, oral, max daily dose 3000 mg (product entry maxDailyDoseAmount 3000 mg). Detailed dosing schedules not specified in the CTIS data.
Target Sample Size
2200
Trial Duration For Participant
730

Stratification factors

  • Prior glucose-lowering drug (GLD) treatment status: Stratum A - drug naïve or ≤4 weeks total GLD treatment; Stratum B - ongoing or previous monotherapy with oral GLD medication >4 weeks

Eligibility

Recruits 2200 Vulnerable population flag selected. Participants must be adults (age > 18 years) and provide signed informed consent. No assent procedures are indicated. Participation requires acceptance of individual data collection from the Swedish National Diabetes Register (NDR) and from SoS/SCB..

Pregnancy Exclusion
Pregnancy or breastfeeding, women of childbearing potential (WOCBP; including perimenopausal women who have had a menstrual period within 1 year) without adequate anticonception during any part of the study period
Vulnerable Population
Vulnerable population flag selected. Participants must be adults (age > 18 years) and provide signed informed consent. No assent procedures are indicated. Participation requires acceptance of individual data collection from the Swedish National Diabetes Register (NDR) and from SoS/SCB.

Inclusion criteria

  • {"criterion_text":"- Diagnosis of T2D (according to WHO criteria) with less than 4 years duration.\n- Men and women, age > 18 years\n- BMI 18.5 - 45 kg/m2\n- Medication for type 2 diabetes: a) drug naïve, or newly started or short temporary medication (Stratum A: no GLD treatment, except for any ongoing or previous treatment for maximally 4 weeks in total) b) ongoing or previous monotherapy with oral GLD medication for more than 4 weeks in total (Stratum B).\n- Participation in the Swedish National Diabetes Register (NDR) and accepting individual data collection from this register and those of SoS/SCB.\n- Signed informed consent"}

Exclusion criteria

  • {"criterion_text":"- Known or suspected other form of diabetes than type 2\n- Ongoing or >4 weeks in total of any previous treatment for type 2 diabetes with: insulin, GLP-1 receptor agonists, SGLT2 inhibitors or combination of any diabetes medications\n- Medical need for any specific GLD treatment, eg. insulin due to marked hyperglycemia\n- HbA1c >70 mmol/mol for patients on monotherapy. >80 in drug naïve, but a higher HbA1c can be accepted if the current glucose levels imply a rapid trajectory towards acceptable glucose control\n- Contraindication to either metformin or dapagliflozin, or any unacceptable risk with either treatment as assessed by the investigator\n- History of established cardiovascular disease: diagnosis of myocardial infarction, angina pectoris, stroke, lower extremity arterial disease, heart failure or ongoing diabetic foot ulcers.\n- Any serious illness or other condition with short life expectancy (<4 yr)\n- Renal impairment (eGFR <60 ml/min/1,73m2)\n- Any condition, as judged by the investigator, that suggests that the patient will be non-compliant or otherwise unsuitable to study medication or study participation. For example, serious psychiatric or alcohol or substance abuse disorders.\n- Pregnancy or breastfeeding, women of childbearing potential (WOCBP; including perimenopausal women who have had a menstrual period within 1 year) without adequate anticonception during any part of the study period\n- Involvement in the planning and/or conduct of the study\n- Ongoing participation in another clinical trial"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Time to first of: 1. All-cause death 2. Major adverse cardiovascular events (MACE; myocardial infarction, stroke, heart failure) 3. Microvascular events (occurrence or progression of retinopathy, nephropathy, or diabetic foot lesions)","definition_or_measurement_approach":"Time-to-event (time from randomization to first occurrence of any of the listed components: all-cause death, MACE [myocardial infarction, stroke, heart failure], or microvascular events [occurrence/progression of retinopathy, nephropathy, diabetic foot lesions])."}

Secondary endpoints

  • {"endpoint_text":"- Modified composite endpoint with weighted components 1-3 of primary endpoint based on their individual degrees of severity (falling in that order). Ordinal analysis at 2 years of follow-up.","definition_or_measurement_approach":"Ordinal analysis of a weighted composite of the three primary components at 2 years follow-up; components weighted by severity."}
  • {"endpoint_text":"- Time to first event among: individual components of the primary endpoint or initiation of insulin treatment.","definition_or_measurement_approach":"Time-to-event (time from randomization to first occurrence of any individual primary component or initiation of insulin)."}
  • {"endpoint_text":"- Time to first of: non-fatal myocardial infarction, stroke, heart failure, unstable angina or cardiovascular death","definition_or_measurement_approach":"Time-to-event for composite cardiovascular outcome (first occurrence of listed events)."}
  • {"endpoint_text":"- Time to first of: heart failure or cardiovascular death Time to event of death","definition_or_measurement_approach":"Time-to-event for heart failure or cardiovascular death; also time-to-death endpoints."}
  • {"endpoint_text":"- Time to first microvascular event; occurrence or progression of retinopathy, nephropathy, diabetic foot lesions","definition_or_measurement_approach":"Time-to-event for microvascular complications (occurrence or progression of retinopathy, nephropathy, diabetic foot lesions)."}
  • {"endpoint_text":"- Time to initiation of insulin treatment","definition_or_measurement_approach":"Time-to-event to initiation of insulin therapy."}
  • {"endpoint_text":"- Time to any treatment failure, defined as add-on or switch to another GLD","definition_or_measurement_approach":"Time-to-event to treatment failure defined as need for add-on therapy or switching to another glucose-lowering drug (GLD)."}
  • {"endpoint_text":"- Change in: 1) HbA1c 2) total cholesterol 3) LDL- cholesterol 4) HDL-cholesterol 5) Triglycerides 6) Urinary albumin/creatinine ratio 7) BMI 8) Systolic blood pressure 9) Diastolic blood pressure","definition_or_measurement_approach":"Change from baseline in listed laboratory and clinical measures (e.g., HbA1c, lipids, UACR, BMI, blood pressure) measured at scheduled visits/registry data; assessed as continuous change."}
  • {"endpoint_text":"- Diagnosis-based (IDG) costs for all health care during study period plus medication cost","definition_or_measurement_approach":"Health economic endpoint: diagnosis-based costs (IDG) for healthcare and medication during study period, derived from registry/administrative data."}
  • {"endpoint_text":"- Results from RAND-36 and DTSQ questionnaires, 0-2 years after randomization.","definition_or_measurement_approach":"Patient-reported outcomes measured by RAND-36 and Diabetes Treatment Satisfaction Questionnaire (DTSQ) at intervals up to 2 years post-randomization."}
  • {"endpoint_text":"- Occurrence of SAEs (all non-elective hospitalisations or other SAEs).","definition_or_measurement_approach":"Safety endpoint: occurrence of serious adverse events, including all non-elective hospitalisations or other events meeting SAE criteria, captured during study period."}
  • {"endpoint_text":"- Occurrence of diabetes- and treatment-specific SAEs (hospitalisations for diabetes, severe hypoglycaemia, ketoacidosis, lactate acidosis, diabetic coma, amputations, fractures).","definition_or_measurement_approach":"Occurrence of diabetes- and treatment-specific serious adverse events as listed, captured via clinical/registry data."}

Recruitment

Registry Or Advocacy Recruitment
True, Swedish National Diabetes Register (NDR); SoS/SCB
Planned Sample Size
2200
Recruitment Window Months
73
Consent Approach
Signed informed consent is required from participants (inclusion criterion). Subject information and informed consent form (L1_SIS ICF_Adults) is provided for adults. Participants must accept registry data collection (NDR, SoS/SCB). No assent procedures are indicated (participants are adults >18). Languages of consent documents not specified in CTIS data.

Methods

  • Register-based recruitment: participation requires inclusion in and acceptance of individual data collection from the Swedish National Diabetes Register (NDR) and linkage to SoS/SCB registries (explicit in inclusion criteria).
  • Site-based recruitment at participating clinical sites (primary care centres and hospitals) across Sweden (trialSites list of participating regions/centres).

Geography

Total Number Of Sites
35
Total Number Of Participants
2200

Sweden

Earliest CTIS Part Ii Submission Date
07-08-2024
Latest Decision Or Authorization Date
30-08-2024
Processing Time Days
23
Number Of Sites
35
Number Of Participants
2200

Sites

Site Name
Region Norrbotten
Department Name
Arvidsjaurs hälsocentral, 933 83 Arvidsjaur
Principal Investigator Name
Tove Bokrantz
Principal Investigator Email
forskning@norrbotten.se
Contact Person Name
Tove Bokrantz
Contact Person Email
forskning@norrbotten.se
Site Name
Region Dalarna
Department Name
Dalecarlia Clinical Research Center, Torggatan 18, 795 30 Rättvik
Principal Investigator Name
Hans Larnefeldt
Principal Investigator Email
forummellansverige-ucr@uu.se
Contact Person Name
Hans Larnefeldt
Contact Person Email
forummellansverige-ucr@uu.se
Site Name
Region Kronoberg
Department Name
Vårdcentralen Dalbo, Brittsommarvägen 2 B, 352 37 Växjö
Principal Investigator Name
Yasir Mahdi
Principal Investigator Email
fou@kronoberg.se
Contact Person Name
Yasir Mahdi
Contact Person Email
fou@kronoberg.se
Site Name
Region Oestergoetland
Department Name
VC Ekholmen, Ekholmsvägen 7, 589 29 Linköping
Principal Investigator Name
Carl Johan Östgren
Contact Person Name
Carl Johan Östgren
Site Name
Region Dalarna
Department Name
Malungs vårdcentral, Box 64, 782 22 Malung
Principal Investigator Name
Peter Rytter
Principal Investigator Email
forummellansverige-ucr@uu.se
Contact Person Name
Peter Rytter
Contact Person Email
forummellansverige-ucr@uu.se
Site Name
Region Soermland
Department Name
VC Centrum Flen, Drottninggatan 1, 64237 Flen
Principal Investigator Name
Kaj Possler
Principal Investigator Email
forummellansverige-ucr@uu.se
Contact Person Name
Kaj Possler
Contact Person Email
forummellansverige-ucr@uu.se
Site Name
Region Dalarna
Department Name
Norslunds vårdcentral, Kopparvägen 29, 791 42 Falun
Principal Investigator Name
Anna Karls
Principal Investigator Email
forummellansverige-ucr@uu.se
Contact Person Name
Anna Karls
Contact Person Email
forummellansverige-ucr@uu.se
Site Name
Uppsala University Hospital
Department Name
VO Specialmedicin, Endokrinsektionen
Principal Investigator Name
Jan Eriksson
Principal Investigator Email
diabetesforskning@akademiska.se
Contact Person Name
Jan Eriksson
Site Name
Vaestra Goetalandsregionen
Department Name
Närhälsan Dalaberg Vårdcentral, Lövskogsg 8, 451 70 Uddevalla
Principal Investigator Name
Intisar Weheliye
Principal Investigator Email
gothia.forum@vgregion.se
Contact Person Name
Intisar Weheliye
Contact Person Email
gothia.forum@vgregion.se
Site Name
Region Uppsala
Department Name
APC forskning, Nära vård och hälsa. Region Uppsala Ledningskontoret, Kungsgärdet, 751 85 Uppsala
Principal Investigator Name
Mats Martinell
Principal Investigator Email
kliniskaprovningar@akademiska.se
Contact Person Name
Mats Martinell
Site Name
Sahlgrenska University Hospital-Vaestra Goetalandsregionen
Department Name
Lundberglab för diabetes-forskning
Principal Investigator Name
Björn Eliasson
Principal Investigator Email
gothia.forum@vgregion.se
Contact Person Name
Björn Eliasson
Contact Person Email
gothia.forum@vgregion.se
Site Name
Region Oerebro Laen
Department Name
Enheten för kliniska studier, Entre S2, Universitetssjukhuset, 701 85 Örebro
Principal Investigator Name
Stefan Jansson
Principal Investigator Email
etikansokan@regionorebrolan.se
Contact Person Name
Stefan Jansson
Contact Person Email
etikansokan@regionorebrolan.se
Site Name
Vaestra Goetalandsregionen
Department Name
Närhälsan Södra Ryd Vårdcentral, Timmerv 3A, 541 64 Skövde
Principal Investigator Name
Margareta Hellgren
Principal Investigator Email
gothia.forum@vgregion.se
Contact Person Name
Margareta Hellgren
Contact Person Email
gothia.forum@vgregion.se
Site Name
Region Stockholm – SLSO
Department Name
Citydiabetes Serafen, Hantverkargatan 2D, 112 21 Stockholm
Principal Investigator Name
Bengt-Olov Tengmark
Contact Person Name
Bengt-Olov Tengmark
Site Name
Region Stockholm – SLSO
Department Name
Handens vårdcentral, Dalarövägen 6, 136 46 Handen
Principal Investigator Name
Charlotta Jacobsson
Contact Person Name
Charlotta Jacobsson
Site Name
Region Oestergoetland
Department Name
Vårdcentralen Cityhälsan Centrum, Gamla Lasarettsgatan 18, 602 39 Norrköping
Principal Investigator Name
Fredrik H. Nyström
Contact Person Name
Fredrik H. Nyström
Site Name
Region Norrbotten
Department Name
Laponia hälsocentral, Källgatan 14, 982 82 Gällivare
Principal Investigator Name
Roxana Sculeanu
Principal Investigator Email
forskning@norrbotten.se
Contact Person Name
Roxana Sculeanu
Contact Person Email
forskning@norrbotten.se
Site Name
Region Dalarna
Department Name
Vårdcentralen i Vansbro, Moravägen 27, 786 33 Vansbro
Principal Investigator Name
Katarina Link
Principal Investigator Email
forummellansverige-ucr@uu.se
Contact Person Name
Katarina Link
Contact Person Email
forummellansverige-ucr@uu.se
Site Name
Region Vaermland
Department Name
Vårdcentralen Kristinehamn, Solrosbacken 1, 681 80 Kristinehamn
Principal Investigator Name
Carin Krödel Boelke
Principal Investigator Email
region@regionvarmland.se
Contact Person Name
Carin Krödel Boelke
Contact Person Email
region@regionvarmland.se
Site Name
Region Gaevleborg
Department Name
Gävle Strand Hälsoscentral OCH Valbo Hälsocenter, Norra Skeppsbron 13, 803 10 Gävle
Principal Investigator Name
Nicklas Persson
Principal Investigator Email
kliniskaprovningar@regiongavleborg.se
Contact Person Name
Nicklas Persson
Site Name
Region Skane Skanes Universitetssjukhus
Department Name
Klinisk forskningsenhet, Inga Marie Nilssonsgata 22, Plan 5, 205 01 Malmö
Principal Investigator Name
Louise Bennet
Principal Investigator Email
studiesupport.sus@skane.se
Contact Person Name
Louise Bennet
Contact Person Email
studiesupport.sus@skane.se
Site Name
Region Soermland
Department Name
Vårdcentralen Mariefred, Solvändan 3, 647 31 Mariefred
Principal Investigator Name
Henrietta Norman
Principal Investigator Email
forummellansverige-ucr@uu.se
Contact Person Name
Henrietta Norman
Contact Person Email
forummellansverige-ucr@uu.se
Site Name
Region Dalarna
Department Name
Domnarvets vårdcentral, Bergebyv 5 alt Box, 731, 781 27 Borlänge
Principal Investigator Name
Per-Olov Mattson
Principal Investigator Email
forummellansverige-ucr@uu.se
Contact Person Name
Per-Olov Mattson
Contact Person Email
forummellansverige-ucr@uu.se
Site Name
Region Skane Skanes Universitetssjukhus
Department Name
Prövningsenheten Kliniska studier Sverige, Skånes universitetssjukhus, 221 85 Lund
Principal Investigator Name
Louise Hagman Bennet
Principal Investigator Email
studiesupport.sus@skane.se
Contact Person Name
Louise Hagman Bennet
Contact Person Email
studiesupport.sus@skane.se
Site Name
Region Vaesterbotten
Department Name
Storumans Hälsocentral, Backvägen 2, 923 32 Storuman
Principal Investigator Name
Mante Hedman
Contact Person Name
Mante Hedman
Site Name
Region Gotland
Department Name
Hemse vårdcentral, Hagagatan 30, 623 51 Hemse
Principal Investigator Name
Gustaf Jörnérus
Contact Person Name
Gustaf Jörnérus
Site Name
Region Soermland
Department Name
Tunafors vårdcentral, Lundbladsv 6, 631 88 Eskilstuna
Principal Investigator Name
Ban Paulus
Principal Investigator Email
forummellansverige-ucr@uu.se
Contact Person Name
Ban Paulus
Contact Person Email
forummellansverige-ucr@uu.se
Site Name
Stift Carlanderska Sjukhuset
Department Name
Carlanderska sjukhuset, Carlandersparken 1, 405 45 Göterborg
Principal Investigator Name
Felix Lundin
Principal Investigator Email
cmc-info@carlanderska.se
Contact Person Name
Felix Lundin
Contact Person Email
cmc-info@carlanderska.se
Site Name
Region Stockholm – SLSO
Department Name
Centrum för diabetes, Solnavägen 1e, 11365 Stockholm
Principal Investigator Name
Sergiu Catrina
Contact Person Name
Sergiu Catrina
Site Name
Region Joenkoepings Laen
Department Name
Rosenhälsans vårdcentral, Huskvarna vårdcentrum Jönköpingsv. 19, 561 31 Huskvarna
Principal Investigator Name
Maria Samefors
Principal Investigator Email
futurum@rjl.se
Contact Person Name
Maria Samefors
Contact Person Email
futurum@rjl.se
Site Name
Region Oestergoetland
Department Name
VC Kärna, Kärnabrunnsgatan 10, 586 62 Malmslätt
Principal Investigator Name
Karin Rådholm
Contact Person Name
Karin Rådholm
Site Name
Region Vaesterbotten
Department Name
Backens hälsocentral, Box 1442, 901 24 Umeå
Principal Investigator Name
Torbjörn Lundberg
Contact Person Name
Torbjörn Lundberg
Site Name
Region Kronoberg
Department Name
Vårdcentralen Teleborg, Södra Vallviksvägen 1, 35235 Växjö
Principal Investigator Name
Yasir Mahdi
Principal Investigator Email
fou@kronoberg.se
Contact Person Name
Yasir Mahdi
Contact Person Email
fou@kronoberg.se
Site Name
Region Oestergoetland
Department Name
Vikbolandet VC, Bygdevägen 13, 610 24 Vikbolandet
Principal Investigator Name
Staffan Nilsson
Contact Person Name
Staffan Nilsson
Site Name
Capio vardcentral Orust
Department Name
Kaprifolvägen 2E, 473 32 Henån
Principal Investigator Name
Halfdan Hilmarsson
Principal Investigator Email
helpdesk@capio.se
Contact Person Name
Halfdan Hilmarsson
Contact Person Email
helpdesk@capio.se

Sponsor

Primary sponsor

Full Name
Uppsala University
Organisation Type
Educational Institution
Country Of Registered Address
Sweden

Investigational products

Investigational Product Name
DAPAGLIFLOZIN
Active Substance
Dapagliflozin propanediol
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
Oral
Authorisation Status
Authorised
Starting Dose
10 mg
Frequency
Once daily
Maximum Dose
10 mg/day
Investigational Product Name
METFORMIN
Active Substance
Metformin
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
Oral
Authorisation Status
Authorised
Frequency
Daily (schedule not specified)
Maximum Dose
3000 mg/day

Related trials

Other published trials that may interest you.