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NKTR-118

Phase 3

Opioid-Induced Constipation (OIC) | Small molecule | Gastrointestinal |AstraZeneca PLC|Last Updated: Feb 23, 2017

Success Probability

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Market & Valuation

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Trial Design

RandomizedDouble-BlindPLACEBO_CONTROLLED
Total Trials4
Total Enrollment2,498

FDA Designations

No designations recorded

Clinical trial landscape

NKTR-118 · 11 trials · 10 indications

Phase 3 4Phase 2 1Phase 1 6
NCT01395524A 12-week Extension of the Phase III Study (D3820C00004) to Assess the Effect and Safety of NKTR-118 in Patients With Non-cancer-related Pain and Opioid-induced ConstipationOpioid-Induced Constipation (OIC)
COMPLETED302 Analytics
NCT01336205Assessment of Long-term Safety in Patients With Non-cancer-related Pain and Opioid-induced ConstipationOpioid-Induced Constipation (OIC)
COMPLETED844 Analytics
NCT01309841Assessment of Efficacy and Safety in Patients With Non-cancer-related Pain and Opioid-induced ConstipationOpioid-Induced Constipation (OIC)
COMPLETED652 Analytics
NCT01323790Assessment of Efficacy and Safety in Patients With Non-cancer-related Pain and Opioid-induced ConstipationOpioid-Induced Constipation (OIC)
COMPLETED700 Analytics
PHASE3COMPLETED
A 12-week Extension of the Phase III Study (D3820C00004) to Assess the Effect and Safety of NKTR-118 in Patients With Non-cancer-related Pain and Opioid-induced Constipation
Opioid-Induced Constipation (OIC)
NCT01395524302
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PHASE3COMPLETED
Assessment of Long-term Safety in Patients With Non-cancer-related Pain and Opioid-induced Constipation
Opioid-Induced Constipation (OIC)
NCT01336205844
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PHASE3COMPLETED
Assessment of Efficacy and Safety in Patients With Non-cancer-related Pain and Opioid-induced Constipation
Opioid-Induced Constipation (OIC)
NCT01309841652
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PHASE3COMPLETED
Assessment of Efficacy and Safety in Patients With Non-cancer-related Pain and Opioid-induced Constipation
Opioid-Induced Constipation (OIC)
NCT01323790700
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Study Endpoints

Primary Endpoints

Incidence of Patients Experiencing at Least One Adverse Event (AE)
Baseline (Week 0) to end of the follow-up period (Week 14)

The incidence of patients experiencing at least one AE during the randomized treatment and follow-up periods was calculated.

Incidence of Patients Experiencing AEs That Resulted in Discontinuation of Investigational Product (IP)
Baseline (Week 0) to end of the follow-up period (Week 14)

The incidence of patients experiencing AEs that resulted in discontinuation of IP during the randomized treatment or follow-up periods was calculated.

Incidence of Patients Experiencing Severe Adverse Events (SAEs)
Baseline (Week 0) to end of the follow-up period (Week 14)

The incidence of patients experiencing SAEs during the randomized treatment and follow-up periods was calculated.

Response (Responder/Non-responder) to Study Drug During Weeks 1 to 12
Baseline (Week 1) to end of treatment (Week 12)

Responder was defined as having at least 3 spontaneous bowel movements (SBMs)/week with at least 1 SBM/week increase over baseline for at least 9 out of the 12 treatment weeks and 3 out of the last 4 treatment weeks during the double-blind treatment period. An SBM is a bowel movement occurring 24 hours or more since the last use of rescue medication.

Change From Baseline in Spontaneous Bowel Movements (SBMs) Per Week During Week 1
Days 1 through 7

Change from baseline in SBMs/week during Week 1 was defined as SBMs/week during the first week of double-blind study medication (between Visit 4 and Visit 6) minus baseline SBMs/week. Baseline was defined as the average SBMs/week during the 2-week OIC screening period. An SBM was defined as a BM without the use of laxatives in the previous 24 hours as recorded in the e-diary.

Description of the pharmacokinetic(PK) profile for NKTR 118 after co administration of Rifampin in terms of area under the concentration-time curve from time zero (predose) extrapolated to infinity (AUC).
Predose and at 0:15, 0:30, 1, 1:30, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours Day 1 and 13
Description of the PK profile for NKTR 118 in terms of maximum plasma concentration (Cmax), time to Cmax (tmax), half-life (t1/2λz), apparent terminal rate constant (λz).
Predose and at 0:15, 0:30, 1, 1:30, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours Day 1 and 13
Description of the PK profile for NKTR 118 in terms of area under the plasma concentration-time curve from time zero to the time of the last measurable concentration [AUC(0-t)].
Predose and at 0:15, 0:30, 1, 1:30, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours Day 1 and 13
Description of the PK profile for NKTR 118 in terms of area under the plasma concentration-time curve from time zero to 24 hours [AUC(0-24)].
Predose and at 0:15, 0:30, 1, 1:30, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours Day 1 and 13
Description of the PK profile for NKTR 118 in terms of apparent oral clearance (CL/F), and apparent volume of distribution during the terminal phase (Vz/F).
Predose and at 0:15, 0:30, 1, 1:30, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours Day 1 and 13
Description of the pharmacokinetic(PK) profile for NKTR 118 after co administration of Ketaconazole in terms of maximum observed plasma concentration (Cmax), time to Cmax (tmax), apparent terminal half-life (t1/2?z).
Predose and at 0:15, 0:30, 1, 1:30, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours Day 1 and 7
Description of the PK profile for NKTR 118 in terms of apparent terminal rate constant (?z), area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-t)].
Predose and at 0:15, 0:30, 1, 1:30, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours Day 1 and 7
Description of the PK profile for NKTR 118 in terms of area under the plasma concentration-time curve from time zero to 24 hours postdose [AUC(0 24)], area under the plasma concentration-time curve from time zero extrapolated to infinity (AUC
Predose and at 0:15, 0:30, 1, 1:30, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours Day 1 and 7
Description of the PK profile for NKTR 118 in terms of apparent oral clearance from plasma (CL/F), and apparent volume of distribution during the terminal phase (Vz/F)
Predose and at 0:15, 0:30, 1, 1:30, 2, 3, 4, 5, 6, 8, 10, 12, 16, 24, 36, 48, and 72 hours Day 1 and 7
To assess the pharmacokinetics of a single dose of NKTR-118 25 mg by assessment of area under the curve over the time (AUC) and maximum concentration (Cmax)
Duration from predose day 1 to day 6.
Percentage of radioactive dose recovered in urine and feces samples and the total percentage of radioactive dose recovered in both urine and feces
Range of Day 1 until day 10
Concentration of total radioactivity in blood and plasma samples
Range of Day 1 until day 10
Concentration of NKTR-118 in blood and plasma sample
Range of Day 1 until day 10
To evaluate the effect of a single dose of NKTR-118 25 mg and 150 mg on the change in time-matched QTcF intervals compared with placebo
30 days pre-dose through 4 treatment periods and follow up 71 days post dose.
The effect of a single dose of NKTR-118 25 mg and 150 mg on the change in time-matched QTcF intervals compared with placebo
Follow up 71 days post dose.
Investigate the safety and tolerability of NKTR-118 using incidence of Adverse Events

Secondary Endpoints

Change From Baseline in Patient Assessment of Constipation Symptoms Questionnaire (PAC-SYM)
Baseline (prior to treatment) to last on-treatment assessment (up to Week 12)
Change From Baseline in Patient Assessment of Constipation Quality of Life (PAC-QOL)
Baseline (prior to treatment) to last on-treatment assessment (up to Week 12)
Response (Responder/Non-responder) to Study Drug in the LIR Subgroup During Weeks 1 to 12
Baseline (Week 1) to end of treatment (Week 12)
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Study Design & Arms

AllocationRANDOMIZED
MaskingQUADRUPLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
NKTR-118 12.5mgEXPERIMENTAL -
NKTR-118 25mgEXPERIMENTAL -
PlaceboPLACEBO_COMPARATOR -
1EXPERIMENTALOral Treatment
2ACTIVE_COMPARATOROral treatment
3PLACEBO_COMPARATOROral treatment
APLACEBO_COMPARATORPlacebo
BEXPERIMENTALNKTR-118
NKTR-118EXPERIMENTALSingle dose NKTR-118 25 mg on Day 1 only
RifampinACTIVE_COMPARATORRifampin 600 mg once daily on Days 4 to 12
Rifampin/ NKTR-118ACTIVE_COMPARATORRifampin 600 mg plus NKTR-118 25 mg on Day 13
Part 1 - AEXPERIMENTALSingle dose NKTR-118 25 mg on Day 1 only
Part 1 - BACTIVE_COMPARATORKetoconazole 400 mg once daily on Days 4 to 8
Part 1- CACTIVE_COMPARATORKetoconazole 400 mg plus NKTR-118 25 mg on Day 7
Group 1EXPERIMENTALNormal hepatic function, 25 mg NKTR-118 administered orally
Group 2EXPERIMENTALMild hepatic impairment, 25 mg NKTR-118 administered orally
Group 3EXPERIMENTALModerate hepatic impairment, 25 mg NKTR-118 administered orally
[14C] NKTR-118EXPERIMENTAL -
CPLACEBO_COMPARATORNKTR-118 placebo (6x placebo tablets)
DACTIVE_COMPARATORMoxifloxacin (1 x 400 mg tablet)

Interventions

NameTypeDescription
NKTR-118DRUG12.5 mg oral tablet once daily
PlaceboDRUGOral tablet intake once daily
Usual careDRUGAs prescribed by the investigator
RifampinDRUGOral 600 mg
KetoconazoleDRUGOral 400 mg
[14C] NKTR-118DRUGSingle 25 mg oral dose administered on Day 1
moxifloxacinDRUG400 mg tablet
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Eligibility Criteria

Age Range18 Years to 84 Years
SexALL
Healthy VolunteersNo
Study Sites116

Inclusion Criteria: * Must have completed the 12-week study D3820C00004 through Visit 8. * Provision of written informed consent prior to any study-specific procedures. * Men and women who were between the ages of \>18 and \<85 years at the time of the screening visit for study D3820C00004. * Conti...

Countries:United StatesAustraliaGermanySlovakiaBelgiumCroatiaCzechiaHungarySpainSwedenUnited KingdomJapan
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Frequently asked questions about NKTR-118

What is NKTR-118 used for?

NKTR-118 is an investigational small molecule being studied for opioid-induced constipation (OIC), drug-induced constipation, and bioavailability. It has been evaluated in healthy volunteers and in patients with OIC. The drug is in clinical development, with completed trials including a Phase 2 study in OIC patients.

Who makes NKTR-118?

NKTR-118 is being developed by AstraZeneca PLC, which trades under the ticker AZN. The company has conducted clinical trials of NKTR-118 in the United States and Japan.

What phase is NKTR-118 in?

NKTR-118 is in Phase 1 of clinical development. It has completed Phase 1 trials in healthy subjects and a Phase 2 trial in patients with opioid-induced constipation. All four trials listed for NKTR-118 are completed, with no active trials ongoing.

What clinical trials is NKTR-118 in?

NKTR-118 has completed four clinical trials: NCT00600119, a Phase 2 study in patients with opioid-induced constipation; NCT01318655, a Phase 1 ascending dose study in Japanese healthy subjects; NCT01325415, a Phase 1 QTc interval study in healthy males; and NCT01533870, a Phase 1 drug interaction study with rifampin in healthy volunteers.

Is NKTR-118 the same as oral PEG-naloxol?

NKTR-118 is also known as oral PEG-naloxol, as referenced in the Phase 2 clinical trial title. It is an investigational drug being studied for opioid-induced constipation.