Trial Outcomes & Findings for Study of Saxagliptin, 5-Hydroxy Saxagliptin, and Metformin Concentrations/Levels in Pediatric Subjects With T2DM (NCT NCT01525225)

Results Overview

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

4 participants

Primary outcome timeframe

Day 1 up to Day 8, plus 30 days

Results posted on

2015-06-22

Participant Flow

Upon approval of Kombiglyze™ XR, the Food and Drug Administration (FDA) required the conduct of this clinical pharmacology study in pediatric patients as a post-marketing requirement (PMR). Study was initiated February 2013. On 14-Nov-13, the FDA issued a letter stating release from this PMR, thus the study was terminated prior to completion.

A total of 4 participants were enrolled. Two participants were treated and completed the study prior to the termination of the study.

Participant milestones

Participant milestones
Measure	Metformin + Saxagliptin + Saxagliptin/Metformin XR FDC Each participant received one dose of a 5 mg saxagliptin tablet once a day (QD) and a 1000 mg Glucophage® immediate release (IR) tablet twice a day (BID) on Day 1. On Days 2 through 6, participants received a 1000 mg tablet of Glucophage® IR BID, and on Day 7, participants received one dose of two 2.5 mg saxagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablets. Finally, on Day 8 participants received four 500 mg Glucophage® IR tablets QD. All study drugs were administered with food.
Enrollment STARTED	4
Enrollment COMPLETED	2
Enrollment NOT COMPLETED	2
Treated STARTED	2
Treated COMPLETED	2
Treated NOT COMPLETED	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Metformin + Saxagliptin + Saxagliptin/Metformin XR FDC Each participant received one dose of a 5 mg saxagliptin tablet once a day (QD) and a 1000 mg Glucophage® immediate release (IR) tablet twice a day (BID) on Day 1. On Days 2 through 6, participants received a 1000 mg tablet of Glucophage® IR BID, and on Day 7, participants received one dose of two 2.5 mg saxagliptin/1000 mg metformin extended release (XR) fixed dose combination (FDC) tablets. Finally, on Day 8 participants received four 500 mg Glucophage® IR tablets QD. All study drugs were administered with food.
Enrollment No longer met study criteria	1
Enrollment Other	1

Baseline Characteristics

Study of Saxagliptin, 5-Hydroxy Saxagliptin, and Metformin Concentrations/Levels in Pediatric Subjects With T2DM

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Metformin + Saxagliptin + Saxagliptin/Metformin XR FDC n=2 Participants Each participant received one dose of a 5 mg saxagliptin tablet once a day (QD) and a 1000 mg Glucophage® IR tablet twice a day (BID) on Day 1. On Days 2 through 6, participants received a 1000 mg tablet of Glucophage® IR BID, and on Day 7, participants received one dose of two 2.5 mg saxagliptin/1000 mg metformin XR FDC tablets. Finally, on Day 8 participants received four 500 mg Glucophage® IR tablets QD. All study drugs were administered with food.
Age, Continuous	13.0 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race/Ethnicity, Customized Black/African American	1 participants n=5 Participants
Race/Ethnicity, Customized White	1 participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 up to Day 8, plus 30 days

Population: All participants who received at least one dose of study drug.

AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible, or missing relationship to study drug.

Outcome measures

Outcome measures
Measure	Metformin + Saxagliptin + Saxagliptin/Metformin XR FDC n=2 Participants Each participant received one dose of a 5 mg saxagliptin tablet once a day (QD) and a 1000 mg Glucophage® IR tablet twice a day (BID) on Day 1. On Days 2 through 6, participants received a 1000 mg tablet of Glucophage® IR BID, and on Day 7, participants received one dose of two 2.5 mg saxagliptin/1000 mg metformin XR FDC tablets. Finally, on Day 8 participants received four 500 mg Glucophage® IR tablets QD. All study drugs were administered with food.
Number of Participants With Adverse Events (AEs) , Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Death AE	2 participants
Number of Participants With Adverse Events (AEs) , Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Death Treatment-Related AE	1 participants
Number of Participants With Adverse Events (AEs) , Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Death AE Leading to Discontinuation	0 participants
Number of Participants With Adverse Events (AEs) , Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Death SAE	0 participants
Number of Participants With Adverse Events (AEs) , Serious Adverse Events (SAEs), AEs Leading to Discontinuation, Death Death	0 participants

SECONDARY outcome

Timeframe: Day 1 to Day 8

Population: Participants who received at least one dose of study drug.

Lower limit of normal (LLN); upper limit of normal (ULN); treatment (RX); pre-treatment (Pre-Rx); units per liter (U/L); millimoles per liter (mmol/L). Alkaline phosphatase U/L:\>1.25\*Pre-RX if Pre-RX \>ULN or \>1.25\*ULN if Pre-RX \<=ULN; aspartate aminotransferase U/L: \>1.25\*Pre-RX if Pre-RX\>ULN or 1.25\*ULN if Pre-RX\<=ULN;alanine aminotransferase U/L: \>1.25\*Pre-RX if Pre-RX\>ULN or 1.25\*ULN if Pre-RX\<=ULN;blood urea nitrogen mmol/L: \>1.1\*ULN if Pre-RX \<=ULN or \>1.2\*Pre-RX if Pre-RX \>ULN; total bilirubin µmol/L: \>1.1\*ULN if Pre-RX \<=ULN or \>1.25\*Pre-RX if Pre-RX \>ULN; creatine phosphokinase U/L: \>1.5\*Pre-RX if Pre-RX\>ULN or \>1.5\*ULN if Pre-RX \<= ULN. Grams per liter (g/L); cells per liter (c/L). Hemoglobin (g/L): \<0.85\* pre-RX; hematocrit (%): \<0.85\*pre-RX;erythrocytes (\*10\^12 c/L): \<0.85\*pre-RX; platelet count (\*10\^9 c/L): \<0.85\*LLN if pre-RX\>=LLN, or if Pre-Tx \<LLN; leukocytes (\*10\^9 c/L): \<0.85\*LLN if pre-RX \<LLN,or \<0.9\*LLN if LLN\<=Pre-RX\<=ULN.

Outcome measures

Outcome measures
Measure	Metformin + Saxagliptin + Saxagliptin/Metformin XR FDC n=2 Participants Each participant received one dose of a 5 mg saxagliptin tablet once a day (QD) and a 1000 mg Glucophage® IR tablet twice a day (BID) on Day 1. On Days 2 through 6, participants received a 1000 mg tablet of Glucophage® IR BID, and on Day 7, participants received one dose of two 2.5 mg saxagliptin/1000 mg metformin XR FDC tablets. Finally, on Day 8 participants received four 500 mg Glucophage® IR tablets QD. All study drugs were administered with food.
Number of Participants With Marked Chemistry or Hematology Laboratory Abnormalities	0 participants

Adverse Events

Metformin + Saxagliptin + Saxagliptin/Metformin XR FDC

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Metformin + Saxagliptin + Saxagliptin/Metformin XR FDC n=2 participants at risk Each participant received one dose of a 5 mg saxagliptin tablet once a day (QD) and a 1000 mg Glucophage® IR tablet twice a day (BID) on Day 1. On Days 2 through 6, participants received a 1000 mg tablet of Glucophage® IR BID, and on Day 7, participants received one dose of two 2.5 mg saxagliptin/1000 mg metformin XR FDC tablets. Finally, on Day 8 participants received four 500 mg Glucophage® IR tablets QD. All study drugs were administered with food.
Nervous system disorders Headache	100.0% 2/2 • Day 1 up to Day 8, plus 30 days. Study initiated February 2013 and was terminated November 2013. Last patient, last visit was June 2013.

Additional Information

Bristol-Myers Squibb Study Director

Bristol-Myers Squibb

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER