Diabetes, Diabetes Mellitus, Type 1
Conditions
Brief summary
The investigators are doing this study to see the effect of insulin degludec in pregnant women with type 1 diabetes, and if it is safe to use. In this study the medicine insulin degludec is compared to another medicine called insulin detemir. Participants will either get insulin degludec or insulin detemir and take it together with a medicine called insulin aspart - which treatment participants get is decided by chance. Participants will get pre-filled insulin pens. Participants will need to take blood sugar measurements several times a day. The study will last between 10 and 25 months depending on whether participants are already pregnant when they join the study. The number of visits and the tests ( for example blood and urine samples and ultrasound scans) the participants will have also depends on whether they are pregnant at study start.
Interventions
DRUGInsulin degludec
Injection for subcutaneous (s.c., under the skin) use once daily. The total trial duration for subjects will be maximum 25 months
DRUGInsulin Aspart
Injection for subcutaneous (s.c., under the skin) use 2-4 times daily with meals. The total trial duration for subjects will be maximum 25 months
DRUGInsulin detemir
Injection for subcutaneous (s.c., under the skin) use, once daily or twice daily. The total trial duration for subjects will be maximum 25 months
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
Sponsor staff involved in the clinical trial is masked according to company standard procedures.
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
- Female, age at least 18 years at the time of signing informed consent - Diagnosed with type 1 diabetes mellitus for at least 1 year prior to the day of screening - Treated with multiple daily subcutaneous insulin injections or continuous subcutaneous insulin infusion (CSII) or inhaled insulin for at least 90 days prior to the day of screening - The subject is planning to become pregnant within 12 months from randomisation and willing to undertake pre-pregnancy counselling or the subject is pregnant with an intrauterine singleton living foetus (gestational week 8 to 13 (+6 days)) without any observed anomalies at randomisation, confirmed by an ultrasound scan - HbA1c at screening below or equal to 8.0% (64 mmol/mol) by central laboratory
Exclusion criteria
- Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening - Pregnant and having proteinuria as evaluated by urine protein-to-creatinine ratio above or equal to 300 mg/g in urine sample measured at screening - Subject being treated or became pregnant with assistance of in vitro fertilisation or other medical infertility treatment - Receipt of any concomitant medication contraindicated in pregnancy according to local label within 28 days before screening and between screening and randomisation for non-pregnant subjects and 28 days before conception and between conception and randomisation for pregnant subjects - Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or pharmacologically dilated fundoscopy performed within the past 90 days prior to randomisation for non-pregnant subjects or within 28 days prior to randomisation for pregnant subjects. - History of severe hyperemesis gravidarum (requiring hospitalisation)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Last Planned Glycosylated Haemoglobin (HbA1c) Prior to Delivery | From GW 16 to GW 36 | Mean of the HbA1c data collected at gestational week (GW) corresponding to last planned visit prior to delivery is presented. This could be either GW 16, 20, 24, 28, 32, 36. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact. On-treatment observation period started at the date of first dose of trial product and ended at the date of the last day on trial product, up to 22 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With HbA1c Below or Equal to 6.5% (48 mmol/Mol) From Last Planned HbA1c Prior to Delivery (Yes/no) | From GW 16 to GW 36 | Number of participants who achieved pre-defined HbA1c targets ≤ 6.5% prior to delivery after GW 16 is presented. In the reported data, 'Yes' infers number of participants who have achieved ≤ 6.5% HbA1c whereas 'No' infers number of participants who have not achieved ≤ 6.5% HbA1c. The endpoint was evaluated based on the data from in-trial observation period which started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact. |
| Last Planned Average Post-prandial Glucose Prior to Delivery (Average of Three Main Meals) | From GW 16 to GW 36 | Mean of post-prandial glucose (PPG) data collected from GW 16 to last planned visit prior to delivery is presented. This could be either GW 16, 20, 24, 28, 32, 36. Average PPG is defined as the average of the available blood glucouse (BG) measurements 90 minutes after breakfast, lunch and main evening meal respectively. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact. |
| Last Planned Fasting Plasma Glucose Prior to Delivery | From GW 16 to GW 36 | Mean of fasting plasma glucose (FPG) data collected from GW 16 to last planned visit prior to delivery is presented. This could be either GW 16, 20, 24, 28, 32, 36. The endpoint was evaluated based on the data from in-trial observation period. The in-trial observation period started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact. |
| Number of Hypoglycaemic Episodes During the Pregnancy Period | From the first day of pregnancy (date of conception) or randomisation to delivery (maximum 23 months) | Number of treatment emergent hypoglycaemic episodes during the pregnancy period is presented. Hypoglycaemic episode (plasma glucose \<= 3.9 mmol/L (70 milligrams per decilitre (mg/dL)) Or \> 3.9 mmol/L (70 mg/dL) occurring in conjunction with hypoglycaemic symptoms) is defined as treatment emergent if the onset of the episode occurs on or after the first day of trial product administration, and no later than 7 days from the last day on trial product. The endpoint was evaluated based on the data from pregnancy period. Pregnancy period started from first day of pregnancy (date of conception corresponding to the first day in GW 2) or randomisation (whichever comes last) to the date of delivery. |
| Number of Participants Who Developed Sight-threatening Retinopathy (Defined as Proliferative Retinopathy or Maculopathy) From Pregnancy Baseline to the End of Treatment (Yes/no) | From pregnancy baseline (corresponding to GW 8-13) to end of treatment (28 days after delivery) | Sight-threatening retinopathy is defined as proliferative retinopathy or maculopathy. Eye examination was performed by fundus photography or pharmacologically dilated fundoscopy to identify if participants have developed sight-threatening retinopathy. The number of participants who developed sight-threatening retinopathy between pregnancy baseline to the end of treatment is presented. In the reported data, 'Yes' infers number of participants who developed sight-threatening retinopathy whereas 'No' infers number of participants who have not developed sight-threatening retinopathy. |
| Number of Participants Who Developed Sight-threatening Retinopathy Defined as Proliferative Retinopathy or Maculopathy From Treatment Baseline to the End of Treatment (Yes/no) | From treatment baseline (week 0) to end of treatment (28 days after delivery) | Sight-threatening retinopathy is defined as proliferative retinopathy or maculopathy. For pregnant women, eye examination was performed by fundus photography or pharmacologically dilated fundoscopy to identify if participants have developed sight-threatening retinopathy. The number of participants who developed sight-threatening retinopathy between treatment baseline to the end of treatment is presented. In the reported data, 'Yes' infers number of participants who developed sight-threatening retinopathy whereas 'No' infers number of participants who have not developed sight-threatening retinopathy. |
| Number of Adverse Events During Pregnancy Period | From the first day of pregnancy (date of conception) or randomisation to delivery (maximum 23 months) | Number of adverse events (AEs) during pregnancy period is reported. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs presented are treatment-emergent AEs (TEAEs). The TEAE is defined as an event that has onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment. |
| Number of Participants With Pre-eclampsia Defined as New-onset Hypertension Occurring From Gestational Week 20 to Delivery and Simultaneous Proteinuria or Presence of Eclampsia, HELLP Syndrome, or Other Severe Organ Involvement (Yes/no) | From GW 20 to delivery | Number of participants with one or more events of pre-eclampsia during pregnancy period is reported. Pre-eclampsia was defined as new-onset hypertension (greater than or equal to) ≥ 140 millimeters of mercury (mmHg) systolic or ≥ 90 mmHg diastolic, based on at least 2 measurements taken at least 4 hours apart) occurring from GW 20 to delivery and simultaneous proteinuria (defined as ≥ 300 mg protein in a 24 hours urine sample, a protein-to-creatinine ratio of ≥ 300 mg/g in a urine sample or a urine dipstick protein of 1+) or presence of eclampsia, haemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome, or other severe organ involvement. In the reported data, 'Yes' infers number of participants who had pre-eclampsia events whereas 'No' infers number of participants who have not had pre-eclampsia events. |
| Number of Participants With Different Modes of Delivery e.g. Vaginal, Operative Vaginal, Planned Caesarean Section or Unplanned Caesarean Section Delivery | At birth | Number of participants who had delivered by which mode of delivery (vaginal, operative vaginal, planned caesarean section or unplanned caesarean section delivery) is presented. Planned caesarean section: decision taken \> 8 hours prior to delivery. Unplanned caesarean section: decision taken ≤ 8 hours prior to delivery. In case of 'early foetal death' or if the participant did not fill the pregnancy outcome form then mode of delivery was reported as 'missing'. |
| Change in Body Weight From Pregnancy Baseline to Last Planned Visit Prior to Delivery | From pregnancy baseline (corresponding to gestational week 8-13) to last planned visit before delivery (last weight recording before given birth) | Change in body weight from pregnancy baseline to last planned visit prior to delivery is presented. |
| Birth Weight for Live Birth Infants | At birth | Mean birth weight for live birth infants is presented. The endpoint was evaluated based on the data from in-trial observation period which started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact. |
| Number of Participants With HbA1c Below or Equal to 6.0% [42 Millimoles Per Mole (mmol/Mol)] From Last Planned HbA1c Prior to Delivery (Yes/no) | From GW 16 to GW 36 | Number of participants who achieved pre-defined HbA1c targets ≤ 6.0% prior to delivery after GW 16 is presented. In the reported data, 'Yes' infers number of participants who have achieved ≤ 6.0% HbA1c whereas 'No' infers number of participants who have not achieved ≤ 6.0% HbA1c. The endpoint was evaluated based on the data from in-trial observation period which started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact. |
| Number of Live Born Infants With Birth Weight < 10th Percentile for Gestational Age and Sex (Local References) (Yes/no) | At birth | Number of live born infants with birth weight \<10th percentile for gestational age and sex is presented.It was assessed using local birth weight percentile curves.The unit of measure 'participants' infers number of live infants.In the reported data,'Yes' infers number of live born infants with birth weight \<10th percentile for gestational age and sex whereas 'No' infers number of live born infants birth weight is not \<10th percentile for gestational age and sex.Unaddressed category refers to the cases where either the parents of the infant had not given consent to share information after delivery or the participants who were withdrawn from trial and they did not give any further information or if the participants did not fill the pregnancy outcome form.Endpoint was evaluated based on the data from in-trial observation period: started at randomization and ended at the date of trial completion,up to 24 months.Date of trial completion:final scheduled follow-up visit (delivery + 58 days). |
| Number of Live Born Infants With Birth Weight > 90th Percentile for Gestational Age and Sex (Local References) [Yes/no] | At birth | Number of live born infants with birth weight \>90th percentile for gestational age and sex is presented.It was assessed using local birth weight percentile curves.The unit of measure 'participants' infers number of live infants. In the reported data,'Yes' infers number of live born infants with birth weight \>90th percentile for gestational age and sex whereas 'No' infers number of live born infants birth weight is not \>90th percentile for gestational age and sex.Unaddressed category refers to cases where either parents of the infant had not given consent to share information after delivery or the participants who were withdrawn from trial and they did not give any further information or if THE participants did not fill the pregnancy outcome form.The endpoint was evaluated based on the data from in-trial observation period:started at randomization and ended at the date of trial completion,up to 24 months. Date of trial completion:final scheduled follow-up visit (delivery + 58 days). |
| Number of Participants With Pre-term Delivery | At birth | Number of pregnant women who had pre-term delivery is presented. Pre-term delivery refers to delivery in \< 37 completed GWs. In the reported data, 'Yes' infers number of participants who had pre-term delivery whereas 'No' infers number of participants who has not had pre-term delivery. Unaddressed category refers to the cases where either the parents of the infant had not given consent to share information after delivery or the participants who were withdrawn from trial and they did not give any further information or if the participants did not fill the pregnancy outcome form. The endpoint was evaluated based on the data from in-trial observation period which started at randomization and ended at the date of trial completion,up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery+58 days). For participants who had not attended the follow-up visit,the date of trial completion was the date of the last participant-investigator contact. |
| Number of Participants With Early Foetal Death (Delivery Before 20 Completed GWs) (Yes/no) | At birth | Number of participants who had early foetal death (delivery before 20 completed GWs) is presented. In the reported data, 'Yes' infers early foetal deaths whereas 'No' infers no foetal deaths. Unaddressed category refers to the cases where either the parents of the infant had not given consent to share information after delivery or the participants who were withdrawn from trial and they did not give any further information or if the participants did not fill the pregnancy outcome form. The endpoint was evaluated based on the data from in-trial observation period which started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact. |
| Number of Participants Who Had Perinatal Mortality (Death of Foetus/Infant ) (Yes/no) | Between at least 20 completed GWs before delivery and before 7 completed days after delivery | Number of participants who had foetal/infant loss at delivery is presented. Perinatal mortality: death of foetus/infant between ≥ 20 completed GWs before delivery and \<1 completed week after delivery). In the reported data, 'Yes' infers early foetal/infant deaths whereas 'No' infers no foetal/infant deaths. Unaddressed category refers to the cases where either the parents of the infant had not given consent to share information after delivery or the participants who were withdrawn from trial and they did not give any further information or if the participants did not fill the pregnancy outcome form. The endpoint was evaluated based on the data from in-trial observation period: started at randomization and ended at the date of trial completion, up to 24 months. Date of trial completion: final scheduled follow-up visit (delivery + 58 days). |
| Number of Participants Who Had Neonatal Mortality (Death of Infant) (Yes/no) | Between at least 7 completed days after delivery and before 28 completed days after delivery | Number of participants who had infant loss after delivery is presented. Neonatal mortality: death of infant between ≥7 completed days after delivery and \< 28 completed days after delivery. In the reported data, 'Yes' infers infant deaths whereas 'No' infers no infant deaths. Unaddressed category refers to the cases where either the parents of the infant had not given consent to share information after delivery or the participants who were withdrawn from trial and they did not give any further information or if the participants did not fill the pregnancy outcome form. The endpoint was evaluated based on the data from in-trial observation period which started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact. |
| Number of Participants With Presence of Major Abnormalities (Classified According to European Concerted Action on Congenital Anomalies and Twins (EUROCAT)) in Their Foetus/Infants | At birth | Number of participants who delivered foetuses/infants with abnormalities (classified according to EUROCAT) is presented. Presence of major abnormalities were based on adjudicated data, as after adjudication congenital anomalies were classified into major or minor anomalies or in other categories. In reported data, 'Yes' infers presence of major abnormalities whereas 'No' infers absence of major abnormalities in foetus/infant. The endpoint was evaluated based on the data from in-trial observation period: started at randomization and ended at the date of trial completion up to 24 months. Date of trial completion : final scheduled follow-up visit (delivery + 58 days). |
| Number of Participants With Live Born Infants (Yes/no) | At birth | Number of participants with live born infants is presented. In the reported data, 'Yes' infers number of live infants whereas 'No' infers early foetal death or termination of pregnancy (induced/elective abortion). The endpoint was evaluated based on the data from in-trial observation period which started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact. |
| Number of Adverse Events in the Infant | From delivery to final follow-up 30 days after delivery | AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. AEs in foetus/infant with particular focus on the AEs from delivery to follow-up are presented. |
| Neonatal Hypoglycaemic Episodes Defined as Plasma Glucose Below or Equal to 1.7 mmol/L (31 mg/dL) or Below or Equal to 2.5 mmol/L (45 mg/dl) (Yes/no) | During between 24 and 48 hours after birth | Number of infants with neonatal hypoglycaemic episodes is presented. Neonatal hypoglycaemic episodes defined as plasma glucose ≤ 1.7 mmol/L (31 mg/dL) during the first 24 hours after birth or below or equal to 2.5 mmol/L (45 mg/dl) between 24 hours and 48 hours after birth. In the reported data, 'Yes' infers number of infants with neonatal hypoglycaemic episodes whereas 'No' infers number of infants with no neonatal hypoglycaemic episodes. Unaddressed category refers to the cases where either the parents of the infant had not given consent to share information after delivery or the participants who were withdrawn from trial and they did not give any further information or if the participants did not fill the pregnancy outcome form. |
| Birth Weight Standard Deviation (SD) Score for Live Birth Infants | At birth | Mean of birth weight SD score for live infants is presented. Birth weight SD score indicates how far an infant's score deviates from the mean of the reference population of same age and same sex born at the same gestational week as per local normal curves. The SD score of 0 indicates that the infants born weigh approximately the same, negative score indicates that the infants born weigh lesser and positive score indicates that the infants born weigh more when compared with the reference population. The endpoint was evaluated based on the data from in-trial observation period which started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact. |
Countries
Argentina, Australia, Austria, Brazil, Canada, Croatia, Denmark, Greece, Ireland, Israel, Italy, Russia, Serbia, Spain, United Kingdom
Participant flow
Recruitment details
The trial was conducted at 56 sites in 14 countries as follows (number of sites that screened participants/number of sites that randomised participants):Argentina (5/4); Australia (7/7); Austria (3/3); Brazil (6/6); Canada (6/5); Croatia (1/1); Denmark (2/2); Greece (3/3); Ireland (2/2); Israel (2/2); Italy (5/5); Russian Federation (8/8); Serbia (2/2) and United Kingdom (8/6).
Pre-assignment details
Based on participant pregnancy status, either non-pregnant with the intention to become pregnant or pregnant from gestational Week (GW) 8-13 + 6 days were randomised in a 1:1 ratio to receive either Insulin Degludec (IDeg) or Insulin Detemir (IDet) in combination with Insulin Aspart (IAsp) as subcutaneous injection.
Participants by arm
| Arm | Count |
|---|---|
| IDeg Participants were to receive IDeg once daily in combination with IAsp 2-4 times daily with meals as subcutaneous injection using FlexTouch and FlexPen pen injectors respectively. After randomization, the IDeg doses were adjusted once weekly to reach the glycaemic target of 4.0 - 5.0 millimoles per liter (mmol/L). It was based on mean of 3 pre-breakfast self-measured plasma glucose (SMPG) values measured on 2 days prior to visit and on the day of the visit. If one of the SMPG values was below target of 4.0 mmol/L, the insulin dose was reduced: (less than) \<3.1 mmol/L: -4 units (U) and 3.1 - 3.9 mmol/L: -2U. If the mean was: 4.0-5.0 mmol/L: no adjustment; 5.1 - 10.0 mmol/L: +2U, 10.1 - 15.0 mmol/L: +4U and (greater than) \>15.0 mmol/L- +6U. On the other hand, for pregnant women, the SMPG was measured 60 minutes after main meal and the IAsp doses were optimized at investigator's discretion based on the participant's SMPG values with target value (less than or equal to) ≤7.8 mmol/L. | 111 |
| IDet Participants were to receive IDet once or twice daily in combination with IAsp 2-4 times daily with meals as subcutaneous injection using FlexPen pen injector. The dose adjustments were made with a glycaemic target of 4.0 - 5.0 mmol/L. Dose adjustments: for IDet once daily - based on mean of 3 pre-breakfast SMPG values; for IDet twice daily - morning doses - based on mean pre-main evening meal SMPG values whereas the evening doses - based on mean pre-breakfast SMPG values. If one of the pre-main evening meal SMPG values were below target of 4.0 mmol/L, the insulin dose was reduced: \<3.1 mmol/L: -4U and 3.1 - 3.9 mmol/L: -2U. If the mean was: 4.0-5.0 mmol/L- no adjustment; 5.1 - 10.0 mmol/L: +2U, 10.1 - 15.0 mmol/L: +4U and \>15.0 mmol/L: +6U. For pregnant, the SMPG was measured 60 minutes after main meal and the IAsp doses were optimized at investigator's discretion based on the participant's SMPG values with target value (less than or equal to) ≤7.8 mmol/L. | 114 |
| Total | 225 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Commencement of medical infertility treatment during the course of the trial | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Non-pregnant subject initiating medication contraindicated during pregnancy | 1 | 1 |
| Overall Study | Randomised non-pregnant did not become pregnant and NOT withdrawn from trial | 6 | 6 |
| Overall Study | Randomised non-pregnant did not become pregnant and withdrawn from trial | 11 | 8 |
| Overall Study | Withdrawal by Subject | 2 | 9 |
Baseline characteristics
| Characteristic | IDet | Total | IDeg |
|---|---|---|---|
| Age, Continuous | 31.1 Years STANDARD_DEVIATION 5.28 | 31.2 Years STANDARD_DEVIATION 5.23 | 31.2 Years STANDARD_DEVIATION 5.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants | 38 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 100 Participants | 187 Participants | 87 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 5 Participants | 9 Participants | 4 Participants |
| Race (NIH/OMB) White | 108 Participants | 214 Participants | 106 Participants |
| Sex: Female, Male Female | 114 Participants | 225 Participants | 111 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 110 | 0 / 112 | 4 / 91 | 7 / 94 |
| other Total, other adverse events | 76 / 110 | 61 / 112 | 17 / 91 | 20 / 94 |
| serious Total, serious adverse events | 38 / 110 | 33 / 112 | 37 / 91 | 42 / 94 |
Outcome results
Primary
Last Planned Glycosylated Haemoglobin (HbA1c) Prior to Delivery
Mean of the HbA1c data collected at gestational week (GW) corresponding to last planned visit prior to delivery is presented. This could be either GW 16, 20, 24, 28, 32, 36. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact. On-treatment observation period started at the date of first dose of trial product and ended at the date of the last day on trial product, up to 22 months.
Time frame: From GW 16 to GW 36
Population: FASpregnant included all randomised pregnant women during the trial. Overall Number of Participants Analyzed = number of participants who contributed to the analysis. Number Analyzed = participants with available data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| IDeg | Last Planned Glycosylated Haemoglobin (HbA1c) Prior to Delivery | in-trial | 6.30 Percentage glycosylated hemoglobin | Standard Deviation 0.7 |
| IDeg | Last Planned Glycosylated Haemoglobin (HbA1c) Prior to Delivery | on-treatment | 6.32 Percentage glycosylated hemoglobin | Standard Deviation 0.69 |
| IDet | Last Planned Glycosylated Haemoglobin (HbA1c) Prior to Delivery | in-trial | 6.26 Percentage glycosylated hemoglobin | Standard Deviation 0.73 |
| IDet | Last Planned Glycosylated Haemoglobin (HbA1c) Prior to Delivery | on-treatment | 6.26 Percentage glycosylated hemoglobin | Standard Deviation 0.71 |
Comparison: Primary Estimand. Imputation of missing data was done within two groups of participants defined by randomised treatment arm based on a multiple imputation approach (x1000). For each of the 1000 imputed datasets last planned HbA1c prior to delivery after GW 16 was analysed using an ANCOVA with treatment, region and the stratification factor as categorical fixed effects and a pregnancy status at randomisation-by-baseline HbA1c interaction.p-value: <0.000195% CI: [-0.31, 0.08]ANCOVA
Comparison: Secondary Estimand. Imputation of missing data was done within two groups of participants defined by randomised treatment arm based on a multiple imputation approach (x1000). For each of the 1000 imputed datasets last planned HbA1c prior to delivery after GW 16 was analysed using an ANCOVA with treatment, region and the stratification factor as categorical fixed effects and a pregnancy status at randomisation-by-baseline HbA1c interaction.p-value: 0.388195% CI: [-0.27, 0.11]ANCOVA
Secondary
Birth Weight for Live Birth Infants
Mean birth weight for live birth infants is presented. The endpoint was evaluated based on the data from in-trial observation period which started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact.
Time frame: At birth
Population: Infants who were born to FASpregnant women are included. FASpregnant is equal to randomised women who were pregnant during the trial. Overall Number of Participants Analyzed = infants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg | Birth Weight for Live Birth Infants | 3691.0 grams (g) | Standard Deviation 628.01 |
| IDet | Birth Weight for Live Birth Infants | 3490.2 grams (g) | Standard Deviation 629.94 |
Secondary
Birth Weight Standard Deviation (SD) Score for Live Birth Infants
Mean of birth weight SD score for live infants is presented. Birth weight SD score indicates how far an infant's score deviates from the mean of the reference population of same age and same sex born at the same gestational week as per local normal curves. The SD score of 0 indicates that the infants born weigh approximately the same, negative score indicates that the infants born weigh lesser and positive score indicates that the infants born weigh more when compared with the reference population. The endpoint was evaluated based on the data from in-trial observation period which started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact.
Time frame: At birth
Population: Infants who were born to FASpregnant women are included. FASpregnant is equal to randomised women who were pregnant during the trial. Overall Number of Participants Analyzed = infants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg | Birth Weight Standard Deviation (SD) Score for Live Birth Infants | 1.7 Standard Deviation score | Standard Deviation 1.2 |
| IDet | Birth Weight Standard Deviation (SD) Score for Live Birth Infants | 1.2 Standard Deviation score | Standard Deviation 1.22 |
Secondary
Change in Body Weight From Pregnancy Baseline to Last Planned Visit Prior to Delivery
Change in body weight from pregnancy baseline to last planned visit prior to delivery is presented.
Time frame: From pregnancy baseline (corresponding to gestational week 8-13) to last planned visit before delivery (last weight recording before given birth)
Population: SASpregnant included all randomised women exposed to at least one dose of trial product and who were pregnant during the trial. Overall Number of Participants Analyzed = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg | Change in Body Weight From Pregnancy Baseline to Last Planned Visit Prior to Delivery | 11.97 Kilogram (Kg) | Standard Deviation 4.79 |
| IDet | Change in Body Weight From Pregnancy Baseline to Last Planned Visit Prior to Delivery | 10.81 Kilogram (Kg) | Standard Deviation 4.55 |
Secondary
Last Planned Average Post-prandial Glucose Prior to Delivery (Average of Three Main Meals)
Mean of post-prandial glucose (PPG) data collected from GW 16 to last planned visit prior to delivery is presented. This could be either GW 16, 20, 24, 28, 32, 36. Average PPG is defined as the average of the available blood glucouse (BG) measurements 90 minutes after breakfast, lunch and main evening meal respectively. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact.
Time frame: From GW 16 to GW 36
Population: FASpregnant included all randomised pregnant women during the trial. Overall Number of Participants Analyzed = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg | Last Planned Average Post-prandial Glucose Prior to Delivery (Average of Three Main Meals) | 7.37 mmol/L | Standard Deviation 1.35 |
| IDet | Last Planned Average Post-prandial Glucose Prior to Delivery (Average of Three Main Meals) | 6.96 mmol/L | Standard Deviation 1.63 |
Secondary
Last Planned Fasting Plasma Glucose Prior to Delivery
Mean of fasting plasma glucose (FPG) data collected from GW 16 to last planned visit prior to delivery is presented. This could be either GW 16, 20, 24, 28, 32, 36. The endpoint was evaluated based on the data from in-trial observation period. The in-trial observation period started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact.
Time frame: From GW 16 to GW 36
Population: FASpregnant which included all randomised pregnant women during the trial. Overall Number of Participants Analyzed = participants with available data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IDeg | Last Planned Fasting Plasma Glucose Prior to Delivery | 6.17 mmol/L | Standard Deviation 2.05 |
| IDet | Last Planned Fasting Plasma Glucose Prior to Delivery | 6.79 mmol/L | Standard Deviation 2.47 |
Secondary
Neonatal Hypoglycaemic Episodes Defined as Plasma Glucose Below or Equal to 1.7 mmol/L (31 mg/dL) or Below or Equal to 2.5 mmol/L (45 mg/dl) (Yes/no)
Number of infants with neonatal hypoglycaemic episodes is presented. Neonatal hypoglycaemic episodes defined as plasma glucose ≤ 1.7 mmol/L (31 mg/dL) during the first 24 hours after birth or below or equal to 2.5 mmol/L (45 mg/dl) between 24 hours and 48 hours after birth. In the reported data, 'Yes' infers number of infants with neonatal hypoglycaemic episodes whereas 'No' infers number of infants with no neonatal hypoglycaemic episodes. Unaddressed category refers to the cases where either the parents of the infant had not given consent to share information after delivery or the participants who were withdrawn from trial and they did not give any further information or if the participants did not fill the pregnancy outcome form.
Time frame: During between 24 and 48 hours after birth
Population: Infants who were born to FASpregnant women are included. FASpregnant is equal to randomised women who were pregnant during the trial. Overall Number of Participants Analyzed = infants with available data.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| IDeg | Neonatal Hypoglycaemic Episodes Defined as Plasma Glucose Below or Equal to 1.7 mmol/L (31 mg/dL) or Below or Equal to 2.5 mmol/L (45 mg/dl) (Yes/no) | During the first 24 hours after birth | Yes | 20 Participants |
| IDeg | Neonatal Hypoglycaemic Episodes Defined as Plasma Glucose Below or Equal to 1.7 mmol/L (31 mg/dL) or Below or Equal to 2.5 mmol/L (45 mg/dl) (Yes/no) | During the first 24 hours after birth | No | 64 Participants |
| IDeg | Neonatal Hypoglycaemic Episodes Defined as Plasma Glucose Below or Equal to 1.7 mmol/L (31 mg/dL) or Below or Equal to 2.5 mmol/L (45 mg/dl) (Yes/no) | During the first 24 hours after birth | Unaddressed category | 2 Participants |
| IDeg | Neonatal Hypoglycaemic Episodes Defined as Plasma Glucose Below or Equal to 1.7 mmol/L (31 mg/dL) or Below or Equal to 2.5 mmol/L (45 mg/dl) (Yes/no) | Between 24 hours and 48 hours after birth | Yes | 4 Participants |
| IDeg | Neonatal Hypoglycaemic Episodes Defined as Plasma Glucose Below or Equal to 1.7 mmol/L (31 mg/dL) or Below or Equal to 2.5 mmol/L (45 mg/dl) (Yes/no) | Between 24 hours and 48 hours after birth | No | 77 Participants |
| IDeg | Neonatal Hypoglycaemic Episodes Defined as Plasma Glucose Below or Equal to 1.7 mmol/L (31 mg/dL) or Below or Equal to 2.5 mmol/L (45 mg/dl) (Yes/no) | Between 24 hours and 48 hours after birth | Unaddressed category | 5 Participants |
| IDet | Neonatal Hypoglycaemic Episodes Defined as Plasma Glucose Below or Equal to 1.7 mmol/L (31 mg/dL) or Below or Equal to 2.5 mmol/L (45 mg/dl) (Yes/no) | Between 24 hours and 48 hours after birth | No | 78 Participants |
| IDet | Neonatal Hypoglycaemic Episodes Defined as Plasma Glucose Below or Equal to 1.7 mmol/L (31 mg/dL) or Below or Equal to 2.5 mmol/L (45 mg/dl) (Yes/no) | During the first 24 hours after birth | Yes | 19 Participants |
| IDet | Neonatal Hypoglycaemic Episodes Defined as Plasma Glucose Below or Equal to 1.7 mmol/L (31 mg/dL) or Below or Equal to 2.5 mmol/L (45 mg/dl) (Yes/no) | Between 24 hours and 48 hours after birth | Yes | 5 Participants |
| IDet | Neonatal Hypoglycaemic Episodes Defined as Plasma Glucose Below or Equal to 1.7 mmol/L (31 mg/dL) or Below or Equal to 2.5 mmol/L (45 mg/dl) (Yes/no) | During the first 24 hours after birth | No | 65 Participants |
| IDet | Neonatal Hypoglycaemic Episodes Defined as Plasma Glucose Below or Equal to 1.7 mmol/L (31 mg/dL) or Below or Equal to 2.5 mmol/L (45 mg/dl) (Yes/no) | Between 24 hours and 48 hours after birth | Unaddressed category | 2 Participants |
| IDet | Neonatal Hypoglycaemic Episodes Defined as Plasma Glucose Below or Equal to 1.7 mmol/L (31 mg/dL) or Below or Equal to 2.5 mmol/L (45 mg/dl) (Yes/no) | During the first 24 hours after birth | Unaddressed category | 1 Participants |
Secondary
Number of Adverse Events During Pregnancy Period
Number of adverse events (AEs) during pregnancy period is reported. An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs presented are treatment-emergent AEs (TEAEs). The TEAE is defined as an event that has onset date on or after the first day of exposure to randomised treatment and no later than 7 days after the last day of randomised treatment.
Time frame: From the first day of pregnancy (date of conception) or randomisation to delivery (maximum 23 months)
Population: SASpregnant included all randomised women exposed to at least one dose of trial product and who were pregnant during the trial.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDeg | Number of Adverse Events During Pregnancy Period | 429 Events |
| IDet | Number of Adverse Events During Pregnancy Period | 328 Events |
Secondary
Number of Adverse Events in the Infant
AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. AEs in foetus/infant with particular focus on the AEs from delivery to follow-up are presented.
Time frame: From delivery to final follow-up 30 days after delivery
Population: Infants who were born to SASpregnant women are included. SASpregnant were randomised women exposed to at least one dose of trial product and who were pregnant during the trial. Overall Number of Participants Analyzed = infants with available data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDeg | Number of Adverse Events in the Infant | 164 Events |
| IDet | Number of Adverse Events in the Infant | 150 Events |
Secondary
Number of Hypoglycaemic Episodes During the Pregnancy Period
Number of treatment emergent hypoglycaemic episodes during the pregnancy period is presented. Hypoglycaemic episode (plasma glucose \<= 3.9 mmol/L (70 milligrams per decilitre (mg/dL)) Or \> 3.9 mmol/L (70 mg/dL) occurring in conjunction with hypoglycaemic symptoms) is defined as treatment emergent if the onset of the episode occurs on or after the first day of trial product administration, and no later than 7 days from the last day on trial product. The endpoint was evaluated based on the data from pregnancy period. Pregnancy period started from first day of pregnancy (date of conception corresponding to the first day in GW 2) or randomisation (whichever comes last) to the date of delivery.
Time frame: From the first day of pregnancy (date of conception) or randomisation to delivery (maximum 23 months)
Population: SASpregnant included all randomised women exposed to at least one dose of trial product and who were pregnant during the trial.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| IDeg | Number of Hypoglycaemic Episodes During the Pregnancy Period | 5431 Episodes |
| IDet | Number of Hypoglycaemic Episodes During the Pregnancy Period | 5982 Episodes |
Secondary
Number of Live Born Infants With Birth Weight < 10th Percentile for Gestational Age and Sex (Local References) (Yes/no)
Number of live born infants with birth weight \<10th percentile for gestational age and sex is presented.It was assessed using local birth weight percentile curves.The unit of measure 'participants' infers number of live infants.In the reported data,'Yes' infers number of live born infants with birth weight \<10th percentile for gestational age and sex whereas 'No' infers number of live born infants birth weight is not \<10th percentile for gestational age and sex.Unaddressed category refers to the cases where either the parents of the infant had not given consent to share information after delivery or the participants who were withdrawn from trial and they did not give any further information or if the participants did not fill the pregnancy outcome form.Endpoint was evaluated based on the data from in-trial observation period: started at randomization and ended at the date of trial completion,up to 24 months.Date of trial completion:final scheduled follow-up visit (delivery + 58 days).
Time frame: At birth
Population: Infants who were born to FASpregnant women are included. FASpregnant is equal to randomised women who were pregnant during the trial. Overall Number of Participants Analyzed = infants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IDeg | Number of Live Born Infants With Birth Weight < 10th Percentile for Gestational Age and Sex (Local References) (Yes/no) | Yes | 1 Participants |
| IDeg | Number of Live Born Infants With Birth Weight < 10th Percentile for Gestational Age and Sex (Local References) (Yes/no) | No | 84 Participants |
| IDeg | Number of Live Born Infants With Birth Weight < 10th Percentile for Gestational Age and Sex (Local References) (Yes/no) | Unaddressed | 1 Participants |
| IDet | Number of Live Born Infants With Birth Weight < 10th Percentile for Gestational Age and Sex (Local References) (Yes/no) | Yes | 3 Participants |
| IDet | Number of Live Born Infants With Birth Weight < 10th Percentile for Gestational Age and Sex (Local References) (Yes/no) | No | 81 Participants |
| IDet | Number of Live Born Infants With Birth Weight < 10th Percentile for Gestational Age and Sex (Local References) (Yes/no) | Unaddressed | 1 Participants |
Secondary
Number of Live Born Infants With Birth Weight > 90th Percentile for Gestational Age and Sex (Local References) [Yes/no]
Number of live born infants with birth weight \>90th percentile for gestational age and sex is presented.It was assessed using local birth weight percentile curves.The unit of measure 'participants' infers number of live infants. In the reported data,'Yes' infers number of live born infants with birth weight \>90th percentile for gestational age and sex whereas 'No' infers number of live born infants birth weight is not \>90th percentile for gestational age and sex.Unaddressed category refers to cases where either parents of the infant had not given consent to share information after delivery or the participants who were withdrawn from trial and they did not give any further information or if THE participants did not fill the pregnancy outcome form.The endpoint was evaluated based on the data from in-trial observation period:started at randomization and ended at the date of trial completion,up to 24 months. Date of trial completion:final scheduled follow-up visit (delivery + 58 days).
Time frame: At birth
Population: Infants who were born to FASpregnant women are included. FASpregnant is equal to randomised women who were pregnant during the trial. Overall Number of Participants Analyzed = infants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IDeg | Number of Live Born Infants With Birth Weight > 90th Percentile for Gestational Age and Sex (Local References) [Yes/no] | Yes | 55 Participants |
| IDeg | Number of Live Born Infants With Birth Weight > 90th Percentile for Gestational Age and Sex (Local References) [Yes/no] | No | 30 Participants |
| IDeg | Number of Live Born Infants With Birth Weight > 90th Percentile for Gestational Age and Sex (Local References) [Yes/no] | Unaddressed | 1 Participants |
| IDet | Number of Live Born Infants With Birth Weight > 90th Percentile for Gestational Age and Sex (Local References) [Yes/no] | Yes | 43 Participants |
| IDet | Number of Live Born Infants With Birth Weight > 90th Percentile for Gestational Age and Sex (Local References) [Yes/no] | No | 41 Participants |
| IDet | Number of Live Born Infants With Birth Weight > 90th Percentile for Gestational Age and Sex (Local References) [Yes/no] | Unaddressed | 1 Participants |
Secondary
Number of Participants Who Developed Sight-threatening Retinopathy (Defined as Proliferative Retinopathy or Maculopathy) From Pregnancy Baseline to the End of Treatment (Yes/no)
Sight-threatening retinopathy is defined as proliferative retinopathy or maculopathy. Eye examination was performed by fundus photography or pharmacologically dilated fundoscopy to identify if participants have developed sight-threatening retinopathy. The number of participants who developed sight-threatening retinopathy between pregnancy baseline to the end of treatment is presented. In the reported data, 'Yes' infers number of participants who developed sight-threatening retinopathy whereas 'No' infers number of participants who have not developed sight-threatening retinopathy.
Time frame: From pregnancy baseline (corresponding to GW 8-13) to end of treatment (28 days after delivery)
Population: SASpregnant included all randomised women exposed to at least one dose of trial product and who were pregnant during the trial
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| IDeg | Number of Participants Who Developed Sight-threatening Retinopathy (Defined as Proliferative Retinopathy or Maculopathy) From Pregnancy Baseline to the End of Treatment (Yes/no) | Left eye | Yes | 2 Participants |
| IDeg | Number of Participants Who Developed Sight-threatening Retinopathy (Defined as Proliferative Retinopathy or Maculopathy) From Pregnancy Baseline to the End of Treatment (Yes/no) | Left eye | No | 79 Participants |
| IDeg | Number of Participants Who Developed Sight-threatening Retinopathy (Defined as Proliferative Retinopathy or Maculopathy) From Pregnancy Baseline to the End of Treatment (Yes/no) | Left eye | Missing | 10 Participants |
| IDeg | Number of Participants Who Developed Sight-threatening Retinopathy (Defined as Proliferative Retinopathy or Maculopathy) From Pregnancy Baseline to the End of Treatment (Yes/no) | Right eye | Yes | 2 Participants |
| IDeg | Number of Participants Who Developed Sight-threatening Retinopathy (Defined as Proliferative Retinopathy or Maculopathy) From Pregnancy Baseline to the End of Treatment (Yes/no) | Right eye | No | 79 Participants |
| IDeg | Number of Participants Who Developed Sight-threatening Retinopathy (Defined as Proliferative Retinopathy or Maculopathy) From Pregnancy Baseline to the End of Treatment (Yes/no) | Right eye | Missing | 10 Participants |
| IDet | Number of Participants Who Developed Sight-threatening Retinopathy (Defined as Proliferative Retinopathy or Maculopathy) From Pregnancy Baseline to the End of Treatment (Yes/no) | Right eye | No | 79 Participants |
| IDet | Number of Participants Who Developed Sight-threatening Retinopathy (Defined as Proliferative Retinopathy or Maculopathy) From Pregnancy Baseline to the End of Treatment (Yes/no) | Left eye | Yes | 2 Participants |
| IDet | Number of Participants Who Developed Sight-threatening Retinopathy (Defined as Proliferative Retinopathy or Maculopathy) From Pregnancy Baseline to the End of Treatment (Yes/no) | Right eye | Yes | 2 Participants |
| IDet | Number of Participants Who Developed Sight-threatening Retinopathy (Defined as Proliferative Retinopathy or Maculopathy) From Pregnancy Baseline to the End of Treatment (Yes/no) | Left eye | No | 79 Participants |
| IDet | Number of Participants Who Developed Sight-threatening Retinopathy (Defined as Proliferative Retinopathy or Maculopathy) From Pregnancy Baseline to the End of Treatment (Yes/no) | Right eye | Missing | 13 Participants |
| IDet | Number of Participants Who Developed Sight-threatening Retinopathy (Defined as Proliferative Retinopathy or Maculopathy) From Pregnancy Baseline to the End of Treatment (Yes/no) | Left eye | Missing | 13 Participants |
Secondary
Number of Participants Who Developed Sight-threatening Retinopathy Defined as Proliferative Retinopathy or Maculopathy From Treatment Baseline to the End of Treatment (Yes/no)
Sight-threatening retinopathy is defined as proliferative retinopathy or maculopathy. For pregnant women, eye examination was performed by fundus photography or pharmacologically dilated fundoscopy to identify if participants have developed sight-threatening retinopathy. The number of participants who developed sight-threatening retinopathy between treatment baseline to the end of treatment is presented. In the reported data, 'Yes' infers number of participants who developed sight-threatening retinopathy whereas 'No' infers number of participants who have not developed sight-threatening retinopathy.
Time frame: From treatment baseline (week 0) to end of treatment (28 days after delivery)
Population: SASpregnant included all randomised women exposed to at least one dose of trial product and who were pregnant during the trial.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| IDeg | Number of Participants Who Developed Sight-threatening Retinopathy Defined as Proliferative Retinopathy or Maculopathy From Treatment Baseline to the End of Treatment (Yes/no) | Left eye | Yes | 2 Participants |
| IDeg | Number of Participants Who Developed Sight-threatening Retinopathy Defined as Proliferative Retinopathy or Maculopathy From Treatment Baseline to the End of Treatment (Yes/no) | Left eye | No | 79 Participants |
| IDeg | Number of Participants Who Developed Sight-threatening Retinopathy Defined as Proliferative Retinopathy or Maculopathy From Treatment Baseline to the End of Treatment (Yes/no) | Left eye | Missing | 10 Participants |
| IDeg | Number of Participants Who Developed Sight-threatening Retinopathy Defined as Proliferative Retinopathy or Maculopathy From Treatment Baseline to the End of Treatment (Yes/no) | Right eye | Yes | 2 Participants |
| IDeg | Number of Participants Who Developed Sight-threatening Retinopathy Defined as Proliferative Retinopathy or Maculopathy From Treatment Baseline to the End of Treatment (Yes/no) | Right eye | No | 79 Participants |
| IDeg | Number of Participants Who Developed Sight-threatening Retinopathy Defined as Proliferative Retinopathy or Maculopathy From Treatment Baseline to the End of Treatment (Yes/no) | Right eye | Missing | 10 Participants |
| IDet | Number of Participants Who Developed Sight-threatening Retinopathy Defined as Proliferative Retinopathy or Maculopathy From Treatment Baseline to the End of Treatment (Yes/no) | Right eye | No | 79 Participants |
| IDet | Number of Participants Who Developed Sight-threatening Retinopathy Defined as Proliferative Retinopathy or Maculopathy From Treatment Baseline to the End of Treatment (Yes/no) | Left eye | Yes | 2 Participants |
| IDet | Number of Participants Who Developed Sight-threatening Retinopathy Defined as Proliferative Retinopathy or Maculopathy From Treatment Baseline to the End of Treatment (Yes/no) | Right eye | Yes | 2 Participants |
| IDet | Number of Participants Who Developed Sight-threatening Retinopathy Defined as Proliferative Retinopathy or Maculopathy From Treatment Baseline to the End of Treatment (Yes/no) | Left eye | No | 79 Participants |
| IDet | Number of Participants Who Developed Sight-threatening Retinopathy Defined as Proliferative Retinopathy or Maculopathy From Treatment Baseline to the End of Treatment (Yes/no) | Right eye | Missing | 13 Participants |
| IDet | Number of Participants Who Developed Sight-threatening Retinopathy Defined as Proliferative Retinopathy or Maculopathy From Treatment Baseline to the End of Treatment (Yes/no) | Left eye | Missing | 13 Participants |
Secondary
Number of Participants Who Had Neonatal Mortality (Death of Infant) (Yes/no)
Number of participants who had infant loss after delivery is presented. Neonatal mortality: death of infant between ≥7 completed days after delivery and \< 28 completed days after delivery. In the reported data, 'Yes' infers infant deaths whereas 'No' infers no infant deaths. Unaddressed category refers to the cases where either the parents of the infant had not given consent to share information after delivery or the participants who were withdrawn from trial and they did not give any further information or if the participants did not fill the pregnancy outcome form. The endpoint was evaluated based on the data from in-trial observation period which started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact.
Time frame: Between at least 7 completed days after delivery and before 28 completed days after delivery
Population: FASpregnant is equal to randomised women who were pregnant during the trial. Overall Number of Participants Analyzed = participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IDeg | Number of Participants Who Had Neonatal Mortality (Death of Infant) (Yes/no) | Yes | 0 Participants |
| IDeg | Number of Participants Who Had Neonatal Mortality (Death of Infant) (Yes/no) | No | 91 Participants |
| IDeg | Number of Participants Who Had Neonatal Mortality (Death of Infant) (Yes/no) | Unaddressed | 1 Participants |
| IDet | Number of Participants Who Had Neonatal Mortality (Death of Infant) (Yes/no) | Yes | 0 Participants |
| IDet | Number of Participants Who Had Neonatal Mortality (Death of Infant) (Yes/no) | No | 92 Participants |
| IDet | Number of Participants Who Had Neonatal Mortality (Death of Infant) (Yes/no) | Unaddressed | 4 Participants |
Secondary
Number of Participants Who Had Perinatal Mortality (Death of Foetus/Infant ) (Yes/no)
Number of participants who had foetal/infant loss at delivery is presented. Perinatal mortality: death of foetus/infant between ≥ 20 completed GWs before delivery and \<1 completed week after delivery). In the reported data, 'Yes' infers early foetal/infant deaths whereas 'No' infers no foetal/infant deaths. Unaddressed category refers to the cases where either the parents of the infant had not given consent to share information after delivery or the participants who were withdrawn from trial and they did not give any further information or if the participants did not fill the pregnancy outcome form. The endpoint was evaluated based on the data from in-trial observation period: started at randomization and ended at the date of trial completion, up to 24 months. Date of trial completion: final scheduled follow-up visit (delivery + 58 days).
Time frame: Between at least 20 completed GWs before delivery and before 7 completed days after delivery
Population: FASpregnant included all randomised women who were pregnant during the trial.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IDeg | Number of Participants Who Had Perinatal Mortality (Death of Foetus/Infant ) (Yes/no) | Yes | 0 Participants |
| IDeg | Number of Participants Who Had Perinatal Mortality (Death of Foetus/Infant ) (Yes/no) | No | 91 Participants |
| IDeg | Number of Participants Who Had Perinatal Mortality (Death of Foetus/Infant ) (Yes/no) | Unaddressed | 1 Participants |
| IDet | Number of Participants Who Had Perinatal Mortality (Death of Foetus/Infant ) (Yes/no) | Yes | 0 Participants |
| IDet | Number of Participants Who Had Perinatal Mortality (Death of Foetus/Infant ) (Yes/no) | No | 92 Participants |
| IDet | Number of Participants Who Had Perinatal Mortality (Death of Foetus/Infant ) (Yes/no) | Unaddressed | 4 Participants |
Secondary
Number of Participants With Different Modes of Delivery e.g. Vaginal, Operative Vaginal, Planned Caesarean Section or Unplanned Caesarean Section Delivery
Number of participants who had delivered by which mode of delivery (vaginal, operative vaginal, planned caesarean section or unplanned caesarean section delivery) is presented. Planned caesarean section: decision taken \> 8 hours prior to delivery. Unplanned caesarean section: decision taken ≤ 8 hours prior to delivery. In case of 'early foetal death' or if the participant did not fill the pregnancy outcome form then mode of delivery was reported as 'missing'.
Time frame: At birth
Population: SASpregnant included all randomised women exposed to at least one dose of trial product and who were pregnant during the trial.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IDeg | Number of Participants With Different Modes of Delivery e.g. Vaginal, Operative Vaginal, Planned Caesarean Section or Unplanned Caesarean Section Delivery | Planned caesarean section | 42 Participants |
| IDeg | Number of Participants With Different Modes of Delivery e.g. Vaginal, Operative Vaginal, Planned Caesarean Section or Unplanned Caesarean Section Delivery | Non planned caesarean section | 23 Participants |
| IDeg | Number of Participants With Different Modes of Delivery e.g. Vaginal, Operative Vaginal, Planned Caesarean Section or Unplanned Caesarean Section Delivery | Operative vaginal birth | 8 Participants |
| IDeg | Number of Participants With Different Modes of Delivery e.g. Vaginal, Operative Vaginal, Planned Caesarean Section or Unplanned Caesarean Section Delivery | Missing | 7 Participants |
| IDeg | Number of Participants With Different Modes of Delivery e.g. Vaginal, Operative Vaginal, Planned Caesarean Section or Unplanned Caesarean Section Delivery | Spontaneous vaginal birth | 11 Participants |
| IDet | Number of Participants With Different Modes of Delivery e.g. Vaginal, Operative Vaginal, Planned Caesarean Section or Unplanned Caesarean Section Delivery | Missing | 7 Participants |
| IDet | Number of Participants With Different Modes of Delivery e.g. Vaginal, Operative Vaginal, Planned Caesarean Section or Unplanned Caesarean Section Delivery | Spontaneous vaginal birth | 18 Participants |
| IDet | Number of Participants With Different Modes of Delivery e.g. Vaginal, Operative Vaginal, Planned Caesarean Section or Unplanned Caesarean Section Delivery | Planned caesarean section | 45 Participants |
| IDet | Number of Participants With Different Modes of Delivery e.g. Vaginal, Operative Vaginal, Planned Caesarean Section or Unplanned Caesarean Section Delivery | Operative vaginal birth | 9 Participants |
| IDet | Number of Participants With Different Modes of Delivery e.g. Vaginal, Operative Vaginal, Planned Caesarean Section or Unplanned Caesarean Section Delivery | Non planned caesarean section | 15 Participants |
Secondary
Number of Participants With Early Foetal Death (Delivery Before 20 Completed GWs) (Yes/no)
Number of participants who had early foetal death (delivery before 20 completed GWs) is presented. In the reported data, 'Yes' infers early foetal deaths whereas 'No' infers no foetal deaths. Unaddressed category refers to the cases where either the parents of the infant had not given consent to share information after delivery or the participants who were withdrawn from trial and they did not give any further information or if the participants did not fill the pregnancy outcome form. The endpoint was evaluated based on the data from in-trial observation period which started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact.
Time frame: At birth
Population: FASpregnant included all randomised women who were pregnant during the trial.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IDeg | Number of Participants With Early Foetal Death (Delivery Before 20 Completed GWs) (Yes/no) | Yes | 4 Participants |
| IDeg | Number of Participants With Early Foetal Death (Delivery Before 20 Completed GWs) (Yes/no) | No | 87 Participants |
| IDeg | Number of Participants With Early Foetal Death (Delivery Before 20 Completed GWs) (Yes/no) | Unaddressed | 1 Participants |
| IDet | Number of Participants With Early Foetal Death (Delivery Before 20 Completed GWs) (Yes/no) | Yes | 5 Participants |
| IDet | Number of Participants With Early Foetal Death (Delivery Before 20 Completed GWs) (Yes/no) | No | 87 Participants |
| IDet | Number of Participants With Early Foetal Death (Delivery Before 20 Completed GWs) (Yes/no) | Unaddressed | 4 Participants |
Secondary
Number of Participants With HbA1c Below or Equal to 6.0% [42 Millimoles Per Mole (mmol/Mol)] From Last Planned HbA1c Prior to Delivery (Yes/no)
Number of participants who achieved pre-defined HbA1c targets ≤ 6.0% prior to delivery after GW 16 is presented. In the reported data, 'Yes' infers number of participants who have achieved ≤ 6.0% HbA1c whereas 'No' infers number of participants who have not achieved ≤ 6.0% HbA1c. The endpoint was evaluated based on the data from in-trial observation period which started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact.
Time frame: From GW 16 to GW 36
Population: FASpregnant included all randomised pregnant women during the trial. Overall Number of Participants Analyzed = participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IDeg | Number of Participants With HbA1c Below or Equal to 6.0% [42 Millimoles Per Mole (mmol/Mol)] From Last Planned HbA1c Prior to Delivery (Yes/no) | Yes | 36 Participants |
| IDeg | Number of Participants With HbA1c Below or Equal to 6.0% [42 Millimoles Per Mole (mmol/Mol)] From Last Planned HbA1c Prior to Delivery (Yes/no) | No | 48 Participants |
| IDet | Number of Participants With HbA1c Below or Equal to 6.0% [42 Millimoles Per Mole (mmol/Mol)] From Last Planned HbA1c Prior to Delivery (Yes/no) | Yes | 31 Participants |
| IDet | Number of Participants With HbA1c Below or Equal to 6.0% [42 Millimoles Per Mole (mmol/Mol)] From Last Planned HbA1c Prior to Delivery (Yes/no) | No | 53 Participants |
Secondary
Number of Participants With HbA1c Below or Equal to 6.5% (48 mmol/Mol) From Last Planned HbA1c Prior to Delivery (Yes/no)
Number of participants who achieved pre-defined HbA1c targets ≤ 6.5% prior to delivery after GW 16 is presented. In the reported data, 'Yes' infers number of participants who have achieved ≤ 6.5% HbA1c whereas 'No' infers number of participants who have not achieved ≤ 6.5% HbA1c. The endpoint was evaluated based on the data from in-trial observation period which started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact.
Time frame: From GW 16 to GW 36
Population: FASpregnant included all randomised pregnant women during the trial. Overall Number of Participants Analyzed = participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IDeg | Number of Participants With HbA1c Below or Equal to 6.5% (48 mmol/Mol) From Last Planned HbA1c Prior to Delivery (Yes/no) | Yes | 58 Participants |
| IDeg | Number of Participants With HbA1c Below or Equal to 6.5% (48 mmol/Mol) From Last Planned HbA1c Prior to Delivery (Yes/no) | No | 26 Participants |
| IDet | Number of Participants With HbA1c Below or Equal to 6.5% (48 mmol/Mol) From Last Planned HbA1c Prior to Delivery (Yes/no) | Yes | 53 Participants |
| IDet | Number of Participants With HbA1c Below or Equal to 6.5% (48 mmol/Mol) From Last Planned HbA1c Prior to Delivery (Yes/no) | No | 31 Participants |
Secondary
Number of Participants With Live Born Infants (Yes/no)
Number of participants with live born infants is presented. In the reported data, 'Yes' infers number of live infants whereas 'No' infers early foetal death or termination of pregnancy (induced/elective abortion). The endpoint was evaluated based on the data from in-trial observation period which started at randomization and ended at the date of trial completion, up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery + 58 days). For participants who had not attended the follow-up visit, the date of trial completion was the date of the last participant-investigator contact.
Time frame: At birth
Population: FASpregnant is equal to randomised women who were pregnant during the trial. Overall Number of Participants Analyzed = participants with available data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IDeg | Number of Participants With Live Born Infants (Yes/no) | No | 5 Participants |
| IDeg | Number of Participants With Live Born Infants (Yes/no) | Yes | 86 Participants |
| IDeg | Number of Participants With Live Born Infants (Yes/no) | Unaddressed | 1 Participants |
| IDet | Number of Participants With Live Born Infants (Yes/no) | Yes | 85 Participants |
| IDet | Number of Participants With Live Born Infants (Yes/no) | No | 7 Participants |
| IDet | Number of Participants With Live Born Infants (Yes/no) | Unaddressed | 4 Participants |
Secondary
Number of Participants With Pre-eclampsia Defined as New-onset Hypertension Occurring From Gestational Week 20 to Delivery and Simultaneous Proteinuria or Presence of Eclampsia, HELLP Syndrome, or Other Severe Organ Involvement (Yes/no)
Number of participants with one or more events of pre-eclampsia during pregnancy period is reported. Pre-eclampsia was defined as new-onset hypertension (greater than or equal to) ≥ 140 millimeters of mercury (mmHg) systolic or ≥ 90 mmHg diastolic, based on at least 2 measurements taken at least 4 hours apart) occurring from GW 20 to delivery and simultaneous proteinuria (defined as ≥ 300 mg protein in a 24 hours urine sample, a protein-to-creatinine ratio of ≥ 300 mg/g in a urine sample or a urine dipstick protein of 1+) or presence of eclampsia, haemolysis, elevated liver enzymes, low platelet count (HELLP) syndrome, or other severe organ involvement. In the reported data, 'Yes' infers number of participants who had pre-eclampsia events whereas 'No' infers number of participants who have not had pre-eclampsia events.
Time frame: From GW 20 to delivery
Population: SASpregnant included all randomised women exposed to at least one dose of trial product and who were pregnant during the trial.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IDeg | Number of Participants With Pre-eclampsia Defined as New-onset Hypertension Occurring From Gestational Week 20 to Delivery and Simultaneous Proteinuria or Presence of Eclampsia, HELLP Syndrome, or Other Severe Organ Involvement (Yes/no) | Yes | 12 Participants |
| IDeg | Number of Participants With Pre-eclampsia Defined as New-onset Hypertension Occurring From Gestational Week 20 to Delivery and Simultaneous Proteinuria or Presence of Eclampsia, HELLP Syndrome, or Other Severe Organ Involvement (Yes/no) | No | 79 Participants |
| IDet | Number of Participants With Pre-eclampsia Defined as New-onset Hypertension Occurring From Gestational Week 20 to Delivery and Simultaneous Proteinuria or Presence of Eclampsia, HELLP Syndrome, or Other Severe Organ Involvement (Yes/no) | Yes | 7 Participants |
| IDet | Number of Participants With Pre-eclampsia Defined as New-onset Hypertension Occurring From Gestational Week 20 to Delivery and Simultaneous Proteinuria or Presence of Eclampsia, HELLP Syndrome, or Other Severe Organ Involvement (Yes/no) | No | 87 Participants |
Secondary
Number of Participants With Presence of Major Abnormalities (Classified According to European Concerted Action on Congenital Anomalies and Twins (EUROCAT)) in Their Foetus/Infants
Number of participants who delivered foetuses/infants with abnormalities (classified according to EUROCAT) is presented. Presence of major abnormalities were based on adjudicated data, as after adjudication congenital anomalies were classified into major or minor anomalies or in other categories. In reported data, 'Yes' infers presence of major abnormalities whereas 'No' infers absence of major abnormalities in foetus/infant. The endpoint was evaluated based on the data from in-trial observation period: started at randomization and ended at the date of trial completion up to 24 months. Date of trial completion : final scheduled follow-up visit (delivery + 58 days).
Time frame: At birth
Population: FASpregnant included all randomised women who were pregnant during the trial.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IDeg | Number of Participants With Presence of Major Abnormalities (Classified According to European Concerted Action on Congenital Anomalies and Twins (EUROCAT)) in Their Foetus/Infants | Yes | 8 Participants |
| IDeg | Number of Participants With Presence of Major Abnormalities (Classified According to European Concerted Action on Congenital Anomalies and Twins (EUROCAT)) in Their Foetus/Infants | No | 84 Participants |
| IDet | Number of Participants With Presence of Major Abnormalities (Classified According to European Concerted Action on Congenital Anomalies and Twins (EUROCAT)) in Their Foetus/Infants | Yes | 8 Participants |
| IDet | Number of Participants With Presence of Major Abnormalities (Classified According to European Concerted Action on Congenital Anomalies and Twins (EUROCAT)) in Their Foetus/Infants | No | 88 Participants |
Secondary
Number of Participants With Pre-term Delivery
Number of pregnant women who had pre-term delivery is presented. Pre-term delivery refers to delivery in \< 37 completed GWs. In the reported data, 'Yes' infers number of participants who had pre-term delivery whereas 'No' infers number of participants who has not had pre-term delivery. Unaddressed category refers to the cases where either the parents of the infant had not given consent to share information after delivery or the participants who were withdrawn from trial and they did not give any further information or if the participants did not fill the pregnancy outcome form. The endpoint was evaluated based on the data from in-trial observation period which started at randomization and ended at the date of trial completion,up to 24 months. The date of trial completion was the date of the final scheduled follow-up visit (delivery+58 days). For participants who had not attended the follow-up visit,the date of trial completion was the date of the last participant-investigator contact.
Time frame: At birth
Population: FASpregnant included all randomised women who were pregnant during the trial.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IDeg | Number of Participants With Pre-term Delivery | Yes | 34 Participants |
| IDeg | Number of Participants With Pre-term Delivery | No | 57 Participants |
| IDeg | Number of Participants With Pre-term Delivery | Unaddressed | 1 Participants |
| IDet | Number of Participants With Pre-term Delivery | Yes | 26 Participants |
| IDet | Number of Participants With Pre-term Delivery | No | 66 Participants |
| IDet | Number of Participants With Pre-term Delivery | Unaddressed | 4 Participants |