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| ID | Type | Description | Link |
|---|---|---|---|
| AP23573-08-901 | Other Identifier | Ariad Protocol Number | |
| MK-8669-038 | Other Identifier | Merck Protocol Number |
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| Name | Class |
|---|---|
| Ariad Pharmaceuticals | INDUSTRY |
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To describe the long-term safety of deforolimus (ridaforolimus, MK-8669) in participants for whom a clinical benefit has been established in a prior parent trial (MK-8669-013, NCT00060645; MK-8669-016, NCT00112372; and MK-8669-028, NCT00704054) with deforolimus and/or in those who remain in long-term follow-up.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ridaforolimus 10 mg Days 1-5 | Experimental | Ridaforolimus 10 mg administered orally once daily on Days 1-5 per week. Participants may continue ridaforolimus intravenous (IV) infusion at the same dose from the parent trial before being switched to ridaforolimus oral tablet. |
|
| Ridaforolimus 10 mg Days 1-6 | Experimental | Ridaforolimus 10 mg administered orally once daily on Days 1-6 per week. Participants may continue ridaforolimus IV infusion at the same dose from the parent trial before being switched to ridaforolimus oral tablet. |
|
| Ridaforolimus 20 mg Days 1-5 | Experimental | Ridaforolimus 20 mg administered orally once daily on Days 1-5 per week. Participants may continue ridaforolimus IV infusion at the same dose from the parent trial before being switched to ridaforolimus oral tablet. |
|
| Ridaforolimus 30 mg Days 1-5 | Experimental | Ridaforolimus 30 mg administered orally once daily on Days 1-5 per week. Participants may continue ridaforolimus IV infusion at the same dose from the parent trial before being switched to ridaforolimus oral tablet. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ridaforolimus Tablet | Drug | Ridaforolimus 10 mg oral tablet |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Who Experienced an Adverse Event | An adverse event is defined as any unintended or undesirable, noxious, or pathological change, compared to pre-existing conditions, experienced by a participant during a clinical study or the follow-up period, regardless of relationship to study drug. The number of participants who experienced an adverse event is presented. | Up to approximately 2991 days, including 30 days after the last dose (through data cut-off date of 03 Apr 2017) |
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event | An adverse event is defined as any unintended or undesirable, noxious, or pathological change, compared to pre-existing conditions, experienced by a participant during a clinical study or the follow-up period, regardless of relationship to study drug. The number of participants who discontinued study drug due to an adverse event is presented. | Up to approximately 2961 days (through data cut-off date of 03 Apr 2017) |
| Measure | Description | Time Frame |
|---|---|---|
| Progression-free Survival (PFS) | PFS was defined as the time from randomization to the first documented progressive disease (PD), or death due to any cause, whichever occurred first. Per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1), PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS for all participants is presented in days. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Director | Merck Sharp & Dohme LLC | Study Director |
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Participants may have continued ridaforolimus IV infusion at the same dose from the parent trial before being switched to ridaforolimus oral tablet.
Participants who continued to receive clinical benefit from ridaforolimus, or who were being followed for long-term safety and efficacy under the following prior protocols were eligible for enrollment into this extension study: MK-8669-013, NCT00060645; MK-8669-016, NCT00112372; and MK-8669-028, NCT00704054.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ridaforolimus 10 mg Days 1-5 | Ridaforolimus 10 mg administered orally once daily on Days 1-5 per week. |
| FG001 | Ridaforolimus 10 mg Days 1-6 | Ridaforolimus 10 mg administered orally once daily on Days 1-6 per week. |
| FG002 | Ridaforolimus 20 mg Days 1-5 | Ridaforolimus 20 mg administered once daily on Days 1-5 per week. |
| FG003 | Ridaforolimus 30 mg Days 1-5 | Ridaforolimus 30 mg administered orally once daily on Days 1-5 per week. |
| FG004 | Ridaforolimus 40 mg Days 1-5 | Ridaforolimus 40 mg administered orally once daily on Days 1-5 per week. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Ridaforolimus 10 mg Days 1-5 | Ridaforolimus 10 mg administered orally once daily on Days 1-5 per week. |
| BG001 | Ridaforolimus 10 mg Days 1-6 | Ridaforolimus 10 mg administered orally once daily on Days 1-6 per week. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Who Experienced an Adverse Event | An adverse event is defined as any unintended or undesirable, noxious, or pathological change, compared to pre-existing conditions, experienced by a participant during a clinical study or the follow-up period, regardless of relationship to study drug. The number of participants who experienced an adverse event is presented. | All participants who received any study drug on this extension protocol according to their actual treatment. | Posted | Count of Participants | Participants | Up to approximately 2991 days, including 30 days after the last dose (through data cut-off date of 03 Apr 2017) |
|
Adverse events were collected in the study database for up to approximately 2991 days (including 30 days after the last dose as of data cut-off date 03 Apr 2017). Following closure of the database through 04 Feb 2018 (approximately 307 days), only serious adverse events were collected.
MedDRA preferred terms "Neoplasm Progression", "Malignant Neoplasm Progression" and "Disease Progression" not related to the drug are excluded. All-cause mortality includes deaths not due to an adverse event. Analysis population includes all participants who received any study drug on this extension protocol according to their actual treatment.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ridaforolimus 10 mg Days 1-5 (Up to Data Cut-Off) | Ridaforolimus 10 mg administered orally once daily on Days 1-5 per week. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Vice President, Global Clinical Development | Merck Sharp & Dohme Corp. | 1-800-672-6372 | ClinicalTrialsDisclosure@merck.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 1, 2008 | Apr 3, 2018 | Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| C515074 | ridaforolimus |
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| Ridaforolimus 40 mg Days 1-5 | Experimental | Ridaforolimus 40 mg administered orally once daily on Days 1-5 per week. Participants may continue ridaforolimus IV infusion at the same dose from the parent trial before being switched to ridaforolimus oral tablet. |
|
|
| Ridaforolimus Intravenous (IV) Infusion | Drug | Ridaforolimus IV infusion administered once daily for 5 days every 2 weeks in a 28-day cycle (two 2-week courses equals 1 cycle). |
|
|
| Up to approximately 2961 days (through data cut-off date of 03 Apr 2017) |
| Overall Survival (OS) | OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis will be censored at the date of the last follow-up. | Up to approximately 2991 days (through data cut-off date of 03 Apr 2017) |
| Duration of Response (DOR) | For participants who demonstrated a confirmed response (Completed Response [CR] or Partial Response [PR]) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. | Up to approximately 2961 days (through data cut-off date of 03 Apr 2017) |
| Withdrawal by Subject |
|
| BG002 | Ridaforolimus 20 mg Days 1-5 | Ridaforolimus 20 mg administered once daily on Days 1-5 per week. |
| BG003 | Ridaforolimus 30 mg Days 1-5 | Ridaforolimus 30 mg administered orally once daily on Days 1-5 per week. |
| BG004 | Ridaforolimus 40 mg Days 1-5 | Ridaforolimus 40 mg administered orally once daily on Days 1-5 per week. |
| BG005 | Total | Total of all reporting groups |
| Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Number | Participants |
|
| Ridaforolimus 10 mg Days 1-6 |
Ridaforolimus 10 mg administered orally once daily on Days 1-6 per week. |
| OG002 | Ridaforolimus 20 mg Days 1-5 | Ridaforolimus 20 mg administered once daily on Days 1-5 per week. |
| OG003 | Ridaforolimus 30 mg Days 1-5 | Ridaforolimus 30 mg administered orally once daily on Days 1-5 per week. |
| OG004 | Ridaforolimus 40 mg Days 1-5 | Ridaforolimus 40 mg administered orally once daily on Days 1-5 per week. |
|
|
| Secondary | Progression-free Survival (PFS) | PFS was defined as the time from randomization to the first documented progressive disease (PD), or death due to any cause, whichever occurred first. Per Response Criteria in Solid Tumors version 1.1 (RECIST 1.1), PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS for all participants is presented in days. | All participants who received any study drug on this extension protocol according to their actual treatment. | Posted | Mean | Full Range | Days | Up to approximately 2961 days (through data cut-off date of 03 Apr 2017) |
|
|
|
| Secondary | Overall Survival (OS) | OS is defined as the time from randomization to death due to any cause. Participants without documented death at the time of the final analysis will be censored at the date of the last follow-up. | All participants who received any study drug on this extension protocol according to their actual treatment. | Posted | Mean | Full Range | Days | Up to approximately 2991 days (through data cut-off date of 03 Apr 2017) |
|
|
|
| Primary | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | An adverse event is defined as any unintended or undesirable, noxious, or pathological change, compared to pre-existing conditions, experienced by a participant during a clinical study or the follow-up period, regardless of relationship to study drug. The number of participants who discontinued study drug due to an adverse event is presented. | All participants who received any study drug on this extension protocol according to their actual treatment. | Posted | Count of Participants | Participants | Up to approximately 2961 days (through data cut-off date of 03 Apr 2017) |
|
|
|
| Secondary | Duration of Response (DOR) | For participants who demonstrated a confirmed response (Completed Response [CR] or Partial Response [PR]) per RECIST 1.1, DOR was defined as the time from first documented evidence of CR or PR until disease progression or death. DOR for participants who had not progressed or died at the time of analysis was to be censored at the date of their last tumor assessment. | All participants who received any study drug on this extension protocol according to their actual treatment and who experienced a CR or PR. | Posted | Number | Days | Up to approximately 2961 days (through data cut-off date of 03 Apr 2017) |
|
|
|
| 1 |
| 3 |
| 0 |
| 3 |
| 3 |
| 3 |
| EG001 | Ridaforolimus 10 mg Days 1-6 (Up to Data Cut-Off) | Ridaforolimus 10 mg administered orally once daily on Days 1-6 per week. | 0 | 1 | 1 | 1 | 1 | 1 |
| EG002 | Ridaforolimus 20 mg Days 1-5 (Up to Data Cut-Off) | Ridaforolimus 20 mg administered once daily on Days 1-5 per week. | 0 | 1 | 0 | 1 | 1 | 1 |
| EG003 | Ridaforolimus 30 mg Days 1-5 (Up to Data Cut-Off) | Ridaforolimus 30 mg administered orally once daily on Days 1-5 per week. | 0 | 1 | 0 | 1 | 1 | 1 |
| EG004 | Ridaforolimus 40 mg Days 1-5 (Up to Data Cut-Off) | Ridaforolimus 40 mg administered orally once daily on Days 1-5 per week. | 1 | 1 | 0 | 1 | 1 | 1 |
| EG005 | Ridaforolimus 10 mg Days 1-6 (Post Data Cut-Off) | Participants remaining on treatment after closure of the study database. Ridaforolimus 10 mg administered orally once daily on Days 1-6 per week. | 0 | 1 | 0 | 1 | 0 | 0 |
| EG006 | Ridaforolimus 20 mg Days 1-5 (Post Data Cut-Off) | Participants remaining on treatment after closure of the study database. Ridaforolimus 20 mg administered orally once daily on Days 1-5 per week. | 0 | 1 | 0 | 1 | 0 | 0 |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA 20.0 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | MedDRA 20.0 | Systematic Assessment |
|
| Vertigo positional | Ear and labyrinth disorders | MedDRA 20.0 | Systematic Assessment |
|
| Blepharospasm | Eye disorders | MedDRA 20.0 | Systematic Assessment |
|
| Cataract | Eye disorders | MedDRA 20.0 | Systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA 20.0 | Systematic Assessment |
|
| Abdominal discomfort | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Dental discomfort | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Retching | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Stomatitis | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Toothache | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 20.0 | Systematic Assessment |
|
| Chills | General disorders | MedDRA 20.0 | Systematic Assessment |
|
| Fatigue | General disorders | MedDRA 20.0 | Systematic Assessment |
|
| Injection site haemorrhage | General disorders | MedDRA 20.0 | Systematic Assessment |
|
| Hypersensitivity | Immune system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Seasonal allergy | Immune system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Hordeolum | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Tinea pedis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
|
| Contusion | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
|
| Foot fracture | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
|
| Post-traumatic pain | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA 20.0 | Systematic Assessment |
|
| Chest X-ray abnormal | Investigations | MedDRA 20.0 | Systematic Assessment |
|
| Weight decreased | Investigations | MedDRA 20.0 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
|
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
|
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 20.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Flank pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Pain in jaw | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Hyperaesthesia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Neuropathy peripheral | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Trigeminal neuralgia | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
|
| Depression | Psychiatric disorders | MedDRA 20.0 | Systematic Assessment |
|
| Dysuria | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
|
| Hydronephrosis | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | MedDRA 20.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Rhinitis allergic | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Sinus congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
|
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Dermatitis acneiform | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Nail disorder | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA 20.0 | Systematic Assessment |
|
All unpublished information that the Sponsor gives to the Investigator shall be kept confidential and shall not be published or disclosed to a third party without the prior written consent of the Sponsor.