Research Study to Compare Three Doses of Semaglutide Tablets Taken Once Daily in People With Type 2 Diabetes (PIONEER PLUS)

Novo Nordisk

Status and phase: Completed; Phase 3

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: Oral semaglutide

Study type: Interventional

Funder types: Industry

Identifiers

NCT04707469

2020-000299-39 (Registry Identifier)

U1111-1247-0210 (Other Identifier)

NN9924-4635

Details and patient eligibility

About

This study compares three doses of once daily semaglutide tablets in people with type 2 diabetes who were previously treated with other oral anti-diabetic medicines. Participants will be initiated on the lowest starting dose of 3 mg and gradually increased until they reach the final trial dose of 14 mg, 25 mg or 50 mg once daily semaglutide tablets. The final three doses will be randomized (i.e., decided by chance). Participants will be administered one tablet per day for 68 weeks. Women cannot take part if they are pregnant, breast-feeding or planning to become pregnant during the study period. Women who can get pregnant will be checked for pregnancy via urine tests. Once daily semaglutide tablets (3 mg, 7 mg and 14 mg) are approved for the treatment of type 2 diabetes in the US, in the EU and in some other countries, under the brand name Rybelsus®.

Enrollment: 1,606 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male or female, age above or equal to 18 years at the time of signing informed consent.

• Diagnosed with type 2 diabetes mellitus at least 180 days prior to the day of screening.

• HbA1c of 8.0-10.5% (64-91 mmol/mol) (both inclusive).

• BMI equal to or above 25 kg/m^2

• Stable daily dose(s) for 90 days prior to the day of screening of any of the following treatment regimens:

• No more than 3 of the following oral anti-diabetic drugs and at least 1 marked with a *:

  • Metformin (equal to or above1500 mg or maximum tolerated or effective dose).
  • Sulfonylureas (SU) (equal to or above half of the maximum approved dose according to local label or maximum tolerated or effective dose).
  • Sodium/glucose cotransporter 2 (SGLT2) inhibitors (maximum tolerated dose).

• Dipeptidyl peptidase-4 (DPP-4) inhibitors (maximally indicated dose as per local label).

• Subjects, on treatment with stable dose of DPP-4 inhibitors at inclusion, must be willing to discontinue DPP-4 inhibitor treatment at randomisation (with no wash-out).

Exclusion criteria

• Treatment with any medication indicated for the treatment of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed.
• Renal impairment measured as estimated glomerular filtration rate (eGFR) value of below 30 mL/min/1.73 m^2 according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation as defined by kidney disease improving global outcomes (KDIGO 2012) classification.
• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

1,606 participants in 3 patient groups

Oral semaglutide 50 mg

Experimental group

Description:

Participants will receive once daily semaglutide tablets in a dose escalating manner for 68 weeks: 3 mg (week 1-4), 7 mg (week 5-8), 14 mg (week 9-12), 25 mg (week 13-16) and 50 mg (week 17-68).

Treatment:

Drug: Oral semaglutide

Oral semaglutide 25 mg

Experimental group

Description:

Participants will receive once daily semaglutide tablets in a dose escalating manner for 68 weeks: 3 mg (week 1-4), 7 mg (week 5-8), 14 mg (week 9-12) and 25 mg (week 13-68).

Treatment:

Drug: Oral semaglutide

Oral semaglutide 14 mg

Active Comparator group

Description:

Participants will receive once daily semaglutide tablets in a dose escalating manner for 68 weeks: 3 mg (week 1-4), 7 mg (week 5-8) and 14 mg (week 9-68).

Treatment:

Drug: Oral semaglutide