Delivery Systems, Diabetes, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in the United States of America (USA). The aim of this clinical trial is to assess and compare the effect on blood sugar control of insulin detemir and insulin aspart or insulin detemir alone administered by a insulin pen PDS290 (FlexTouch®) versus a Novo Nordisk marketed insulin pen (FlexPen®) in subjects with type 1 or type 2 diabetes mellitus. Furthermore, the subject's preference of the devices will be investigated by the use of questionnaires.
Interventions
DEVICEFlexTouch®
All subjects to receive insulin detemir treatment (and if relevant insulin aspart) with either a insulin pen PDS290 (FlexTouch®) or a Novo Nordisk marketed insulin pen (FlexPen®) for 12 weeks. After 12 weeks, all subjects will continue their insulin treatment with the other injection device.
DEVICEFlexPen®
All subjects to receive insulin detemir treatment (and if relevant insulin aspart) with either a insulin pen PDS290 (FlexTouch®) or a Novo Nordisk marketed insulin pen (FlexPen®) for 12 weeks. After 12 weeks, all subjects will continue their insulin treatment with the other injection device.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Informed consent obtained before any trial-related activities * Subjects diagnosed with type 1 or type 2 diabetes. If type 2 diabetics, treatment with or without oral anti diabetic medication is allowed * Current users of vial/syringe (pen naïve) treated with short-acting insulin (insulin aspart, glulisine or lispro) and once daily long-acting insulin (detemir or glargine) or once daily long-acting insulin (detemir or glargine) alone * Treatment with insulin (i.e. aspart, glulisine, lispro, detemir or glargine) for at least 6 months * Body Mass Index (BMI) less than 45.0 kg/m\^2 * HbA1c less than or equal to 9.0% at screening visit based on analysis from central laboratory * Able and willing to adhere to the trial-specific insulin regimen for the entire trial period
Exclusion criteria
* Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or inadequate contraceptive techniques during the trial period (adequate contraceptive measures are considered as intrauterine device, oral contraceptives and barrier methods) * Previous participation in this trial (screening visit) * Systemic drugs that may influence glycaemic control (e.g., corticosteroids) * Known or suspected allergy to trial product(s) or related products * Known or suspected abuse of alcohol or drug abuse * Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation * Previous treatment with sitagliptin * Clinically significant, active (or over the past 12 months) disease of the gastrointestinal, neurological, genitourinary, or haematological systems * Cardiac disease defined as: Decompensated heart failure (New York Heart class III or IV, unstable angina pectoris within the past 6 months of study enrolment, myocardial infarction within the past 12 months and a clinically significant history of arrhythmias or conduction delays on electrocardiogram (ECG) over the past 12 months * Any other severe acute or chronic illness as judged by the Investigator * Recurrent major hypoglycaemia (defined as severe central nervous system dysfunction associated with hypoglycaemia, requiring the assistance of another person) or hypoglycaemia unawareness (defined as a condition in which subjects no longer experience the usual warning signs of hypoglycaemia; the symptoms of hypoglycaemia may be different, less pronounced or even absent) or hospitalisation for diabetic ketoacidosis during the previous six months * Any other conditions that the Investigator judges would interfere with trial participation or evaluation of results (i.e. planned any diagnostic or therapeutic medical intervention such as surgery) * Participated in another clinical trial and received an investigational drug within the last 4 weeks
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| HbA1c (Glycosylated Haemoglobin) for Participants Treated With PDS290 and FlexPen® | Week 12 of each treatment sequence |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Summary Score for Treatment Satisfaction | Week 24 | Overall summary from Insulin Treatment Satisfaction Questionnaire (ITSQ) with higher scores (0-100) indicating greater satisfaction. |
| Score for Treatment Impact Measure for Diabetes | Week 24 | Treatment Related Impact Measure for Diabetes (TRIM-D and TRIM-D device) with scores from 0-100, higher scores indicate less treatment related impact. |
| Clinical Technical Complaints (CTCs) | Weeks 0-24 (whole trial period) | A clinical technical complaint is any written, electronic or oral communication that alleges deficiencies related to the identity, quality, durability, reliability, safety or performance of a medical device. |
| Percentage of Subject Having Preference for PDS290 Versus FlexPen® in Terms of Convenience and Ease of Use | Week 24 | Questionnaire (Niskanen Comparative Device Questionnaire) compared preference / convenience and ease of use by device specific questionnaire (summarised by scores of question 9) |
| Number of Adverse Device Effects | From randomisation (week 0) and until 7 days after Week 24 (Visit 16) | Adverse device effects were defined as clinical technical complaints (CTCs) related to an Adverse Event/Serious Adverse Event. This was defined as an adverse unintended reaction to a medical device. This definition includes any event which is caused by an inadequate or incomplete user instruction or guide in the use of the device and any event caused by wrongful use. |
| Hypoglycaemic Episodes, Number of Events Per Subject Day | Weeks 0-12 (first treatment) and 12-24 (second treatment) | — |
| Number of Hypoglycaemic Episodes | Weeks 0-12 (first treatment) and 12-24 (second treatment) | Presented by severity: major: subject not able to treat himself; minor: plasma glucose below 3.1 mmol/L; symptoms only: no plasma glucose measured or above or equal to 3.1 mmol/L. |
Countries
United States
Participant flow
Recruitment details
The trial was conducted at 61 sites in the United States of America (USA).
Pre-assignment details
Screening period of 2 weeks where the subjects were assessed for eligibility, run-in period of 6 weeks, hereafter eligible subjects were randomised to one of the two 12-week treatment sequences: PDS290 -\> FlexPen® or FlexPen® -\> PDS290.
Participants by arm
| Arm | Count |
|---|---|
| Entire Trial Population Participants who in random order received usual insulin treatment with pre-filled pen device PDS290 for 12 weeks followed by switch to pre-filled pen device FlexPen® for 12 weeks or vice versa. The frequency of basal and bolus injections were kept the same throughout the trial. Both prefilled pens were self-administered subcutaneously by the participants. | 242 |
| Total | 242 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 2 | 1 |
| Period 1 | Lack of Efficacy | 0 | 2 |
| Period 1 | Unclassified | 5 | 1 |
| Period 2 | Adverse Event | 0 | 1 |
| Period 2 | Lack of Efficacy | 1 | 0 |
| Period 2 | Protocol Violation | 0 | 3 |
| Period 2 | Unclassified | 2 | 2 |
Baseline characteristics
| Characteristic | Entire Trial Population |
|---|---|
| Age, Continuous | 58 years STANDARD_DEVIATION 13.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 16 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 226 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| HbA1c (glycosylated haemoglobin) | 7.3 percentage (%) of total haemoglobin STANDARD_DEVIATION 0.9 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 29 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants |
| Race (NIH/OMB) White | 199 Participants |
| Region of Enrollment United States | 242 participants |
| Sex: Female, Male Female | 95 Participants |
| Sex: Female, Male Male | 147 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 25 / 238 | 31 / 235 |
| serious Total, serious adverse events | 7 / 238 | 5 / 235 |
Outcome results
Primary
HbA1c (Glycosylated Haemoglobin) for Participants Treated With PDS290 and FlexPen®
Time frame: Week 12 of each treatment sequence
Population: Intention-to-treat (ITT) population comprising all randomised subjects and with data on HbA1c. This was a cross-over trial, so subjects received treatment with both PDS290 and FlexPen®. Results are reported separately for each treatment period, i.e. PDS290 versus FlexPen®). Some subjects dropped out during either treatment sequence.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PDS290 | HbA1c (Glycosylated Haemoglobin) for Participants Treated With PDS290 and FlexPen® | 7.5 percentage (%) of total haemoglobin | Standard Deviation 1 |
| FlexPen® | HbA1c (Glycosylated Haemoglobin) for Participants Treated With PDS290 and FlexPen® | 7.5 percentage (%) of total haemoglobin | Standard Deviation 1 |
Comparison: The null hypothesis is that PDS290 be not non-inferior to FlexPen® with respect to HbA1c after 12 weeks of treatment; non-inferiority margin is 0.4 % (absolute).95% CI: [-0.127, 0.032]Linear mixed effect model
Secondary
Clinical Technical Complaints (CTCs)
A clinical technical complaint is any written, electronic or oral communication that alleges deficiencies related to the identity, quality, durability, reliability, safety or performance of a medical device.
Time frame: Weeks 0-24 (whole trial period)
Population: ITT population. This was a cross-over trial, so subjects received treatment with both PDS290 and FlexPen®. Results are reported separately for each treatment period, i.e. PDS290 versus FlexPen®). Some subjects did not have any available results in PDS290 and FlexPen® treatment groups, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PDS290 | Clinical Technical Complaints (CTCs) | 67 CTCs |
| FlexPen® | Clinical Technical Complaints (CTCs) | 84 CTCs |
Secondary
Hypoglycaemic Episodes, Number of Events Per Subject Day
Time frame: Weeks 0-12 (first treatment) and 12-24 (second treatment)
Population: ITT population. This was a cross-over trial, so subjects received treatment with both PDS290 and FlexPen®. Results are reported separately for each treatment period, i.e. PDS290 versus FlexPen®).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PDS290 | Hypoglycaemic Episodes, Number of Events Per Subject Day | 0.06 events per subject-day |
| FlexPen® | Hypoglycaemic Episodes, Number of Events Per Subject Day | 0.06 events per subject-day |
Secondary
Number of Adverse Device Effects
Adverse device effects were defined as clinical technical complaints (CTCs) related to an Adverse Event/Serious Adverse Event. This was defined as an adverse unintended reaction to a medical device. This definition includes any event which is caused by an inadequate or incomplete user instruction or guide in the use of the device and any event caused by wrongful use.
Time frame: From randomisation (week 0) and until 7 days after Week 24 (Visit 16)
Population: ITT population. This was a cross-over trial, so subjects received treatment with both PDS290 and FlexPen®. Results are reported separately for each treatment period, i.e. PDS290 versus FlexPen®). Some subjects did not have any available results in PDS290 and FlexPen® treatment groups, respectively.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PDS290 | Number of Adverse Device Effects | 0 events |
| FlexPen® | Number of Adverse Device Effects | 0 events |
Secondary
Number of Hypoglycaemic Episodes
Presented by severity: major: subject not able to treat himself; minor: plasma glucose below 3.1 mmol/L; symptoms only: no plasma glucose measured or above or equal to 3.1 mmol/L.
Time frame: Weeks 0-12 (first treatment) and 12-24 (second treatment)
Population: ITT population. This was a cross-over trial, so subjects received treatment with both PDS290 and FlexPen®. Results are reported separately for each treatment period, i.e. PDS290 versus FlexPen®). Some subjects did not have any available results in PDS290 and FlexPen® treatment groups, respectively.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PDS290 | Number of Hypoglycaemic Episodes | Minor episodes | 920 episodes |
| PDS290 | Number of Hypoglycaemic Episodes | Major episodes | 7 episodes |
| PDS290 | Number of Hypoglycaemic Episodes | Symptoms only | 181 episodes |
| PDS290 | Number of Hypoglycaemic Episodes | All episodes | 1108 episodes |
| FlexPen® | Number of Hypoglycaemic Episodes | Symptoms only | 162 episodes |
| FlexPen® | Number of Hypoglycaemic Episodes | Major episodes | 3 episodes |
| FlexPen® | Number of Hypoglycaemic Episodes | Minor episodes | 927 episodes |
| FlexPen® | Number of Hypoglycaemic Episodes | All episodes | 1092 episodes |
Secondary
Percentage of Subject Having Preference for PDS290 Versus FlexPen® in Terms of Convenience and Ease of Use
Questionnaire (Niskanen Comparative Device Questionnaire) compared preference / convenience and ease of use by device specific questionnaire (summarised by scores of question 9)
Time frame: Week 24
Population: ITT population. Some subjects did not have any available Niskanen Comparative Device Questionnaire results.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| PDS290 | Percentage of Subject Having Preference for PDS290 Versus FlexPen® in Terms of Convenience and Ease of Use | Preference of PDS290 | 68 percentage of participants |
| PDS290 | Percentage of Subject Having Preference for PDS290 Versus FlexPen® in Terms of Convenience and Ease of Use | Preference of FlexPen® | 19 percentage of participants |
| PDS290 | Percentage of Subject Having Preference for PDS290 Versus FlexPen® in Terms of Convenience and Ease of Use | No preference | 13 percentage of participants |
Secondary
Score for Treatment Impact Measure for Diabetes
Treatment Related Impact Measure for Diabetes (TRIM-D and TRIM-D device) with scores from 0-100, higher scores indicate less treatment related impact.
Time frame: Week 24
Population: ITT population. This was a cross-over trial, so subjects received treatment with both PDS290 and FlexPen®. Results are reported separately for each treatment period, i.e. PDS290 versus FlexPen®). Some subjects did not have any TRIM-D available results in PDS290 and FlexPen® treatment groups, respectively.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PDS290 | Score for Treatment Impact Measure for Diabetes | TRIM-D total scores | 75.1 scores on a scale | Standard Deviation 13.1 |
| PDS290 | Score for Treatment Impact Measure for Diabetes | TRIM-D device scores | 84.9 scores on a scale | Standard Deviation 12.7 |
| FlexPen® | Score for Treatment Impact Measure for Diabetes | TRIM-D total scores | 72.8 scores on a scale | Standard Deviation 13.6 |
| FlexPen® | Score for Treatment Impact Measure for Diabetes | TRIM-D device scores | 78.6 scores on a scale | Standard Deviation 16.6 |
Secondary
Summary Score for Treatment Satisfaction
Overall summary from Insulin Treatment Satisfaction Questionnaire (ITSQ) with higher scores (0-100) indicating greater satisfaction.
Time frame: Week 24
Population: ITT population. This was a cross-over trial, so subjects received treatment with both PDS290 and FlexPen®. Results are reported separately for each treatment period, i.e. PDS290 versus FlexPen®). Some subjects did not have any available ITSQ results in PDS290 and FlexPen® treatment groups, respectively.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PDS290 | Summary Score for Treatment Satisfaction | 80.9 scores on a scale | Standard Deviation 11.3 |
| FlexPen® | Summary Score for Treatment Satisfaction | 76.8 scores on a scale | Standard Deviation 15.2 |