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Pramlintide · 16 trials · 8 indications
To investigate the clinical utility (change in HbA1c, seven-point glucose profile, body weight, and insulin use) and safety of pramlintide in subjects with type 1 and type 2 diabetes mellitus who have not achieved glycemic targets with insulin therapy.
To collect data regarding the selection of subjects for pramlintide administration by healthcare professionals and to further understand management issues in subjects with type 1 and type 2 diabetes mellitus who have not achieved glycemic targets with insulin therapy
Original study DFA102 (NCT00673387) baseline refers to Visit 5 (Day 1). If Day 1 value was missing or after the first dose date of randomized study medication, the last available value on or prior to Day 1 was used. Least Squares (LS) Mean based on a repeated measures mixed model with treatment, sex, DFA102 baseline BMI category, nominal week, treatment by nominal week interaction as factors, and DFA102 baseline weight value as a covariate, with a heterogeneous compound symmetry error covariance structure within each treatment group. Stable population consists of all ITT participants (received at least one injection of treatment) who had the same treatment group assignment in Study DFA102 and Study DFA102E, ie, ITT participants who were in Study DFA102 treatment groups Placebo, Pramlintide 360 + Metreleptin 1.25, Pramlintide 360 + Metreleptin 2.5 and Pramlintide 360 + Metreleptin 5.0.
Body weight was measured in kilogram (kg). Baseline is defined as Day 1. If Day 1 was missing or after the first dose date of randomized treatment, the last available value prior to Day 1 was used. Drug Randomization stratified by sex and 3 categories baseline BMI (12 arms); 3 treatment arms combined for summaries as single placebo treatment group; 3 combined for summaries as single pramlintide monotherapy treatment group (total: 8 treatment groups).
Absolute change in body weight as measured in kilograms (kg) from baseline to Week 16. Baseline defined as Day 1 of randomized treatment.
To determine the effect of pramlintide on the pharmacokinetics of an orally administered concomitant medication (acetaminophen) when administered at various times in relation to subcutaneous (SC) pramlintide dosing. The noncompartmental plasma acetaminophen pharmacokinetic (PK) parameters used in the analyses are defined as follows: AUC(0-12hr): Area under the plasma acetaminophen concentration-time curve. Cmax : The peak acetaminophen concentrationd. Tmax : Duration from the time of acetaminophen dosing to the time of the first maximum observed concentration, Cmax. t½: Terminal half-life The primary study endpoints include: * pharmacokinetic parameters AUC(0-12 hr) and Cmax of plasma acetaminophen concentrations Secondary Study Endpoints * pharmacokinetic parameters Tmax and t1/2 of plasma acetaminophen concentrations
To assess the acute effect of pramlintide administered subcutaneously (SC) on satiety in normal-weight and obese non-diabetic subjects and in insulin-treated subjects with type 1 and type 2 diabetes. To be measured by Total caloric intake, macronutrient intake (carbohydrate, fat, protein, and other), duration of buffet meal, aand satiety data measured via a satiety assessment at Period 1 (Visit 2) and Period 2 (Visit 3).
To assess the acute effect of pramlintide administered SC on food intake in normal-weight and obese non-diabetic subjects and in insulin-treated subjects with type 1 and type 2 diabetes. To be measured by Total caloric intake, macronutrient intake (carbohydrate, fat, protein, and other), duration of buffet meal, aand satiety data measured via a satiety assessment at Period 1 (Visit 2) and Period 2 (Visit 3).
To determine the effect of various anatomical injection sites and varying needle lengths upon the absolute bioavailability of pramlintide when injected subcutaneously (SC) in non-obese and obese subjects with type 1 and type 2 diabetes mellitus using insulin.
24-hour MWG mg/dL, defined as total area under the 24-hour tissue glucose curve obtained with CGM, divided by actual time span in the 24-hour period.
| Arm | Type | Description |
|---|---|---|
| Pramlintide | EXPERIMENTAL | Pramlintide acetate injection is a clear, colorless, sterile solution for SC injection. It consists of pramlintide in sodium acetate buffer, pH 4.0, containing 43-mg/mL mannitol as an iso-osmolality modifier and 2.25 mg/mL metacresol as a preservative |
| Pramlintide Acetate | ACTIVE_COMPARATOR | Pramlintide acetate injection is a clear, colorless, sterile solution for SC injection. It consists of pramlintide in sodium acetate buffer, pH 4.0, containing 43 mg/mL mannitol as an iso-osmolality modifier and 2.25 mg/mL metacresol as a preservative. The concentration of pramlintide injection to be used in this study is 0.6 mg/mL. |
| Placebo | PLACEBO_COMPARATOR | Placebo injection will be supplied in the same 5-mL multidose glass vials with a rubber stopper.Ingredients: D-Mannitol 43.0 mg/mL Metacresol 2.25 mg/mL Glacial acetic acid 1.53 mg/mL Sodium acetate trihydrate 0.61 mg/mL pH 4.0 Water for injection qs to 5.0 mL |
| Pramlintide Acetate (AC137) | ACTIVE_COMPARATOR | Pramlintide acetate (AC137) injection is a clear, colorless, sterile solution for SC injection. It consists of pramlintide in sodium acetate buffer, pH 4.0, containing 43 mg/mL mannitol as an iso-osmolality modifier and 2.25 mg/mL metacresol as a preservative. The strength of pramlintide injection is 0.6 mg/mL |
| 1 | PLACEBO_COMPARATOR | - |
| 2 | EXPERIMENTAL | Pramlintide and 1.25mg Metreleptin |
| 3 | EXPERIMENTAL | Pramlintide and 2.5mg Metreleptin |
| 4 | EXPERIMENTAL | Pramlintide and 5.0mg Metreleptin |
| Placebo-P + Placebo-M | PLACEBO_COMPARATOR | Placebo matched to pramlintide BID plus placebo matched to metreleptin BID |
| Pramlintide 360 mcg + Placebo-M | EXPERIMENTAL | 360 mcg pramlintide given twice per day (BID) plus Placebo matched to Metreleptin given BID |
| Placebo-P + Metreleptin 5.0 mg | EXPERIMENTAL | Placebo matched to pramlintide BID plus metreleptin 5.0 mg BID |
| Pramlintide 180 mcg + Metreleptin 2.5 mg | EXPERIMENTAL | Pramlintide 180 mcg BID plus Metreleptin 2.5 mg BID |
| Pramlintide 180 mcg + Metreleptin 5.0 mg | EXPERIMENTAL | Pramlintide 180 mcg BID plus Metreleptin 5.0 mg BID |
| Pramlintide 360 mcg + Metreleptin 1.25 mg | EXPERIMENTAL | Pramlintide 360 mcg BID plus Metreleptin 1.25 mg BID |
| Pramlintide 360 mcg + Metreleptin 2.5 mg | EXPERIMENTAL | Pramlintide 360 mcg BID plus Metreleptin 2.5 mg BID |
| Pramlintide 360 mcg + Metreleptin 5.0 mg | EXPERIMENTAL | Pramlintide 360 mcg BID plus Metreleptin 5.0 mg BID |
| Placebo and Metreleptin | EXPERIMENTAL | Placebo-pramlintide 600 microliters (µL) twice a day (BID) and metreleptin (recombinant-methionyl human leptin) 5 milligram (mg) BID, 20 weeks |
| Pramlintide Acetate and Placebo | EXPERIMENTAL | Lead-in period: 2 weeks pramlintide acetate 180 mcg BID, then 2 weeks pramlintide acetate 360 mcg BID Study period: Pramlintide acetate 360 mcg BID and placebo-metreleptin 1 mL BID, 20 weeks |
| Pramlintide Acetate and Metreleptin | EXPERIMENTAL | Lead-in period: 2 weeks pramlintide acetate 180 mcg BID, then 2 weeks pramlintide acetate 360 mcg BID Study period: Pramlintide acetate 360 mcg BID and metreleptin (recombinant-methionyl human leptin) 5 mg BID, 20 weeks |
| Lead-In Period | OTHER | During the Lead-In Period before a participant was randomized to a study arm, the participant received 180 mcg pramlintide acetate twice a day (BID) for 2 weeks, followed by 360 mcg pramlintide acetate BID for 2 weeks (total of 4 weeks in the Lead-In Period). |
| Pramlintide acetate (AC137) injection | EXPERIMENTAL | Pramlintide acetate (AC137) injection is a clear, colorless, sterile solution for injection. It consists of pramlintide in sodium acetate buffer, pH 4.0, containing 43mg/mL mannitol as an iso-osmolality modifier and 2.25 mg/mL metacresol as a preservative. The strength of pramlintide is 1.0 mg/mL for SC injection and 0.6 mg/mL for IV bolus injection. |
| Pramlintide acetate & regular insulin | EXPERIMENTAL | Pramlintide will be adiministered by sc infusion at a concentration of 1000ug/mL |
| Placebo and regular insulin | PLACEBO_COMPARATOR | Placebo is similar sterile solution without pramlintide. |
| Pramlintide 6 mcg per unit of insulin dose | EXPERIMENTAL | The pramlintide dose will be calculated based on the subjects' individual insulin units. Dose ratio to be examined is pramlintide 6 mcg for each unit of insulin. |
| Pramlintide 9 mcg per unit of insulin dose | EXPERIMENTAL | The pramlintide dose will be calculated based on the subjects' individual insulin units. Dose ratio to be examined is pramlintide 9 mcg for each unit of insulin. |
| Pramlintide 12 mcg per unit of insulin dose | EXPERIMENTAL | The pramlintide dose will be calculated based on the subjects' individual insulin units. Dose ratio to be examined is pramlintide 12 mcg for each unit of insulin. |
| Name | Type | Description |
|---|---|---|
| pramlintide acetate | DRUG | Pramlintide (0.6 mg/mL) in 5.0-mL multiple-draw glass vials for SC injection for 12weekes and after Pramlintide (1.0 mg/mL) 1.5 mL pen-cartridge. Subjects who do not switch to the pen-cartridge device at Week 12 will continue to administer pramlintide using a syringe and vial. |
| Placebo | DRUG | The placebo injection will be supplied in the same 5-mL multidose glass vials with a rubber stopper. |
| Pramlintide and Metreleptin | DRUG | Subcutaneous injection, twice daily |
| metreleptin | DRUG | subcutaneous injection, twice a day |
| placebo-P | DRUG | subcutaneous injection, twice a day |
| placebo-M | DRUG | subcutaneous injection, twice a day |
| sibutramine | DRUG | oral tablet, once a day, 10mg |
| phentermine | DRUG | oral tablet, once a day, 37.5mg |
| pramlintide acetate 360 mcg | DRUG | subcutaneous injection, twice a day, 360mcg |
| placebo-pramlintide 600 uL | DRUG | twice a day |
| placebo-metreleptin 1 mL | DRUG | twice a day |
| Pramlintide acetate 180 mcg | DRUG | subcutaneous injection twice a day, 180 mcg |
| Lispro insulin U-100 | DRUG | Subjects will be stabilized on a separate insulin pump and administered lispro insulin throughout the study, except during both inpatient treatment periods (Visit 4 and Visit 5) |
| Regular insulin U-100 | DRUG | Use during two in-patient treatment periods (visits 4 and 5) and administered by separate pump |
Inclusion Criteria: * The subject has a clinical diagnosis of type 1 diabetes mellitus requiring treatment with insulin for a minimum of 6 months at Screening; -OR- The subject has a clinical diagnosis of type 2 diabetes requiring treatment with insulin with or without oral antidiabetic agents for ...
Pramlintide is an investigational small molecule being developed for obesity, overweight, and diabetes mellitus, including non-insulin-dependent (Type 2) and Type 1 diabetes. It is in Phase 2 clinical development and has not been approved by the FDA.
Pramlintide is being developed by AstraZeneca PLC, a biopharmaceutical company listed on the stock exchange under the ticker symbol AZN. The company is conducting clinical trials to evaluate the drug's safety and efficacy in metabolic conditions.
Pramlintide is currently in Phase 2 clinical development. It has completed four clinical trials, including Phase 2 and Phase 3 studies, but it remains investigational and has not received FDA approval for any indication.
Pramlintide has completed four clinical trials, including NCT00042458, a Phase 3 study in Type 1 diabetes; NCT00042471, a Phase 2 bioavailability study; NCT00042601, a Phase 2 study on satiety and food intake; and NCT00107107, a Phase 3 long-term safety study. All trials are completed.
Pramlintide is also known by the brand name Symlin. It is an investigational drug being studied for diabetes and obesity. AstraZeneca is developing it, and it is currently in Phase 2 clinical trials.